Taking into account OTL size of his family, impact should be massive. Until 1526 not much change, but then? Is Ferdinand eventually seek for annulment of his marriage with Anna Jagiellon (risky, considering his struggle for Hungarian throne, pissing of her uncle Sigismund would not be the best idea during war against Janos Zapolya). What would Habsburgs do to discourage Sigismund the Old from supporting Zapolya (IOTL Ferdinand destined his oldest daughter to marry Sigismund's son from the moment of her birth to keep him on his side)? Is HRE Charles V more likely to remarry if his son Philip is the only male heir of vast Habsburg inheritance (Hard to imagine Philip holding everything from Hungary to Spain after death of his father and uncle)?