Yeah...Henri and Bernhardt are both natural 5s and chosen themselves. This seems to be a massive thing that HERO are hiding...natural 5s all basically have to be chosen of some vastly powerful entity and they are all vastly better than serum evolved 5s. This might also be what Dr. Xanthe means when he says that the MC might have already failed a requirement for a natural 5th evolution because the MC's 3rd was basically a serum induced evolution...but he doesn't know about eye origin now connected to the MC.
It might also be precisely what makes a natural 5th evolution so dangerous and why there are trials nobody wants to talk about. Having to face vastly powerful entities who can just erase you from existence on a whim in hopes of gaining their support would make a natural 5th evolution extremely dangerous. Having to fight and potentially defeat a chosen might also be another. Going for a natural 5th evolution would basically guarantee death or success with very low chance of the latter.
The serum isn't a problem, Henri himself comments to Berniboy:
Henri: "They're adapting well to their evolution"
Berniboy: "not as well as we were, the serum is flawed"
Henri: "no, we are just different, you were much stronger than them before you even evolved"
Even the Arbiter comments that Ella and Nico are perfected spawn ("waiting for me are two perfected spawn, engaged in heated battle" is how he refers to both Ella and Nico) when he sees them fighting (in the deadend MC monsterfies in the Battle of Diamond).
The big difference seems to be the process of evolving to 5th, as in the jorney to the evolution or the special conditions to make it happen naturaly, not the serum itself.