There are several ways to make an ADOM game unwinnable.
There are several ways through which the player's actions, an ADOM game can be unfairly rendered unwinnable. Those are:
1. Throwing a potion of exchange at a regular monster who picked up a Chaos orb. The new monster won't drop the items its previous form had on it.
2. Sacrificing a monster (orb guardian) means no fixed drops (orbs) are left.
3. Orbs can be lost in the Pyramid or Minotaur maze if the player drops them there and then can't retrieve them anymore due to their level restrictions.
4. It is possible to throw at "nothing special" squares (i.e. the border of a wilderness location). If the player throws an item at the very border of the screen, it'll get stuck in the first row of "nothing special" squares. Regular items are then unreachable and essentially lost forever. Orbs and other artifacts will hop back into the PC's backpack if not inside a town or other special wilderness location - otherwise, they're also lost. Here's a quick demonstration:
1. Don't let monsters pick Chaos orbs up. Possibly, preserve monster inventories between PoEX transformations.
2. Make sacrificed monsters drop what they would have dropped if killed, besides their other inventory (if any).
3. Make the orbs hop back to the PC's backpack when they're dropped in these locations, like they do in the ID or WE, regardless of the PC's level.
4. Prevent any items from getting stuck in the second row, as it's done when the player attempts to kick or shoot them into the first row.