I'm not sure how well it would work, but it keeps popping up in my head recently, and has some amusing potential, so I thought I'd post the idea in case it inspires someone.
Basically, Tsukune, rather than being turned into a ghoul from Moka's blood, is given Kurumu's blood slightly earlier in the story (although preferably after getting all the girls together, Yukari, Moka, Mizore, and Kurumu), although how that will happen I'm not sure, probably some kind of convoluted accident (one idea I had was a messed up 'kiss' where they both get broken lips and/or bitten tongues in the process). Normally the succubus blood would have to be relatively inert, as otherwise the succubus mates might have trouble if exposed to smaller amounts during intercourse or weird foreplay. Tsukune however is the regular feeding station for a vampire, which has caused his blood production and the way his body reacts to blood levels to start getting a bit weird.
The result? Tsukune wakes up the next morning sore all over, with a painful headache... and now very cute, and female. After some screaming and an escape from the boys dorms, she is eventually identified by someone friendly, so the situation can be figured out.
The transformative effects of Kurumu's blood are permanent on humans, Tsukune is now what is known as a Lillum (maybe some other name...?). They are at first glance like regular girls, if very attractive ones with a weaker version of the succubus charm power. They also can generate youki, but only by processing psychically absorbed sexual energies. This youki can be used for minor strength and speed enhancement, relatively good regeneration, minor telepathic abilities, levitation (although not as good flight as a succubus), and entering and manipulating the dreams of sleeping people. ((Note: If the story becomes longer and more serious, being a lillum shouldn't stop Tsukune from also becoming a Ghoul))
Lillum were created on purpose by succubi in the past who ran things like brothels and strip clubs and dance halls with lots of girls, or sometimes on members of royal harems after being paid to do so. The girls were given an infusion of succubus blood with some triggering elements and became Lillum, which made them more attractive and healthier, although with side effects of often increasing their sex drives and making them somewhat more dangerous, and potentially reducing their life spans a small amount, if their bodies don't react with the blood as well, and cause the detrimental forms of regeneration, rather than the beneficial forms of it which would lengthen their life-spans. This practice has fallen out as the monster world has become more and more hidden from the human world, but they still sometimes turn human servants who want to become such and have served them loyally into Lillum, usually girls, as the succubi usually prefer to keep males men, but if they have other guys they are more interested in, or are a succubi who swings more the other way...
Anyway, Tsukune isn't happy with the change, especially as it means she can never return to her parents and the human world. Moka and Kurumu are throwing the blame between each-other, but both feel a bit of guilt over it, and are upset for Tsukune's sake. Somewhat surprisingly, Tsukune's harem hasn't collapsed (although humorously, each of the remaining girls might think they are the only one still interested), Yukari has always been quite open about being as interested in Moka as Tsukune, and finds Tsukune just as attractive as before to her tastes. For Kurumu, well, she's a succubus, and beyond probably being mildly bisexual, has already somewhat bonded emphatically towards Tsukune as her 'chosen one', a bond likely unaffected by Tsukune becoming a Lillum (in fact, some succubi with tastes going that way have been known to have lillum mates). Mizore was more drawn by Tsukune's personality than looks to begin with. Moka is probably less certain than the others, but isn't unfamiliar with the idea of a girlxgirl relationship, especially given the seemingly incestuous interests of some of her sisters. They all of course choose to comfort Tsukune, weather or not they are still interested that way (and at least one of them should still be) and reassure her that they are still at least friends and they will support Tsukune in her change and help her adjust to her new life.
Might be an interesting way to do a Yukari pairing, as those seem to be uncommon, and Yukari is the most clearly bisexual of the girls, although I'd be a bit worried about her going to far and not being sympathetic enough about the changes and trauma Tsukune is likely going through.
There is also the matter of Tsukune's cover with the school, either Tsukune will have to re-enroll under a new identity, or they'll have to explain the change somehow without revealing that Tsukune used to be human. Perhaps they'll claim Tsukune is some kind of shapeshifting monster (doppleganger?) with no real gender except personal choice, and had initially been using a male form, but recently changed her mind to be female? I'm guessing the new identity would work better though, although a few people might see through it to generate incidents as they realize that the girls aren't shaken up by Tsukune's disappearance and a similar girl has replaced him in their group, and that Tsukune used to be a human boy and is now a lillum.