Gary could also be the one to cause Ash's heartbreak. Maybe Gary outshines Ash in a big Pokemon battle and then mocks him for it. This could make Ash feel like a failure and break his heart. Gary has always been a bit of a rival to Ash, so this kind of situation is plausible in fanfiction.
A new, powerful villain could be the cause. This villain might target Ash's Pokémon and manage to steal them all away. Ash would be heartbroken not only because he lost his Pokémon but also because he feels he has failed to protect them.
It could be Annabeth. Maybe they had a huge fight over something important, like the future of their relationship or a difference in their values regarding their demigod duties. And this fight led to Annabeth leaving Percy, which broke his heart.
Another possibility is that the Pokemon themselves could be the cause, in an unexpected way. For example, if one of Satoshi's Pokemon gets seriously ill and needs to be left in a far - away place for treatment. Satoshi decides to stay with the Pokemon, but Haruka has to continue her journey. This difficult decision could lead to heartbreak for both of them.
Another character could be Kakashi. Maybe he has to make a tough decision that goes against Fem Naruto's wishes. For example, not allowing her to go on a dangerous mission she really wants to. This could make Fem Naruto feel betrayed and heartbroken, as Kakashi is a respected figure in her life.
It could be his arch - enemy. For instance, the Joker might play a cruel trick on Nightwing that makes him lose someone he cares about deeply, thus causing his heartbreak.
It could be that there is some misunderstanding between them. Say, Misty misinterprets something Ash does as him not caring about her anymore. Ash, being clueless about her misinterpretation, doesn't correct it in time. Then Misty distances herself from him, and Ash is left heartbroken when he finally realizes what has happened.
It could be a rival trainer who has feelings for May and tries to drive a wedge between her and Ash. This rival might spread false rumors about Ash to make May doubt him, leading to Ash's heartbreak.
Misty is a very likely candidate. She has been with Ash from the early days of his journey. They have a deep bond and have shared many adventures together. Their relationship has always had a bit of a romantic undertone, so in a fanfiction, it would make perfect sense for them to get married.
One common theme is unrequited love. Maybe Ash has feelings for a character who doesn't feel the same way back. Another could be betrayal. For example, a friend or a loved one betrays Ash, which leads to his heartbreak. Also, the theme of loss can be present, like losing a Pokemon that was very close to him, which shatters his heart in the fanfiction.
Well, perhaps in the fanfiction, Ash is betrayed by a group of friends he trusted deeply. They might have used him to get access to some rare Pokémon or some important information, and then they turn their backs on him. This would be a huge heartbreak for Ash, who is always so loyal to his friends. Or it could be that he fails to achieve a major goal like winning a big Pokémon tournament due to some unfair circumstances, and he feels heartbroken as all his efforts seem to be in vain.