April 1497 - Margarethe of Austria married Juan of Aragon, prince de los Asturias
September 1497 - Isabel of Aragon weds Manuel, king of Portugal
Juan, prince de los Asturias dies
December 1497 - Margarethe gives birth to Juan's posthumous stillborn daughter.
August 1498 - Isabel gives birth to Miguel da Paz. Dies in childbirth. Her son survives.
Margarethe was a widow when Manuel went shopping for his second wife. It was hardly as though Isabel hadn't done her dury - he had a son and heir to represent an alliance with Spain, although Miguel died in July 1500, and Manuel wed Maria in October 1500. So, what if he were to marry Margarethe instead (let's assume for argument's sake she WASN'T rendered sterile by the birth of her daughter) on a slightly accelerated pace.
Let's assume it CAN happen (Fernando-Isabel are raw from their son, granddaughter and now daughter's deaths in a year. Margarethe is a bad reminder to them of this. Isabel's son is still around, so they decide Margarethe goes to Lisbon instead). How would Maximilian, Fernando and Isabel feel about this? Especially if Miguel still dies young?