Well, certainly hemophilia was a chance they took when they had their children. But neither the Imperial Couple, Ella or anyone else could have predicted the tidal wave that seemed to happen with the appearance of Rasputin. So in reality, those that knew that Alix could be obstinate and single-minded, nobody could have forseen that the coming of Rasputin would be the harbinger of the end of the Empire. Certainly, the couple themselves didn't see it.
But that's another topic. Rasputin was only the tip of a 300 year old iceberg.
IMO, had the war and distance not seperated the sisters, and had Alix not have isolated herself so much, perhaps she would have found some sort of support system, something she clearly needed - as any parent of a disabled or dying child does. Had Irene been the one in Russia, would it have made any difference?