I had the exact same issue, but on a later generation, something like the 7th one (quest was reproduce with a giantess, which I already had in another run without problem), I assumed it was because of my min/maxing (always going for 2 upgrades each gen) that triggered the issue, but if that happened in your 4th gen it isn't probable. Did you manage to find a way to fix that in the end ?
Also, on a secondary note, After completing the game 2 times, I was wondering about a few things :
-What is the thing with the Angel talks and the Demon related achievements ? I never saw any of this things in game, my second run seemed to have cultists doing sacrifices but, even when letting them do it a lot of times it didn't seem to trigger anything special.
-What power does the golden head possess ? The power to see the unseen and to hear the sound of gold, did someone figure it out ?