User blog comment:The Milkman/The Writing of the Ending/@comment-5503561-20120529183511/@comment-1388547-20120530040927

After all the ways the story may have diverged over the course of the Mass Effect series, especially in ME3, I'd say it would be extremely difficult to have anything set in the ME galaxy for the next few hundred or thousand years after ME3. Consider:


 * The rachni have as many as four different permutations depending on whether the player killed them in ME1 and ME3, though the main difference is probably just between saving the queen in both games versus letting her die in either.


 * The krogan might have been cured of the genophage and be ready to expand again, or they might still have a low birth rate. If the genophage was cured, they might have enlightened leaders (Wrex and possibly Bakara) who will work to prevent the problems of the past from arising again, or they might have a traditionalist (Wreav) who is probably trouble for everybody else in the galaxy.


 * The quarians may have been wiped out, or they may have reclaimed Rannoch. Similarly, the geth may have been wiped out, either by the quarians or by the red space magic in the Destroy ending.  If the player sided with the geth and let the quarians die, then later chose the Destroy ending, Rannoch might even be deserted.


 * If the player chose the Synthesis ending, all life in the galaxy might have been turned into some kind of synthetic/organic hybrid by green space magic.

If they're going to make anything after this, it'll probably have to be something that can be decoupled from all these decisions -- either a prequel that comes before ME3, and preferably before the whole trilogy, or something set in a place so isolated that none of these events have touched it, or a sequel set so far in the future that they can handwave away the decisions made by the player. (Hey, maybe the rachni go extinct even if Shep saves them both times, or maybe the krogan evolve a way to breed while infected with the genophage -- it's implied that was happening anyway -- or maybe the there's a quarian-like cyborg race of indeterminate origin now living on Rannoch...)

Anyway, while the ending of ME3 was certainly left open to interpretation, it was definitely not left open for sequels, follow-ons, or ridiculous MMOs.