I always keep 22 players. In extreme case, I can put 11 different players in different formations. Then in almost all cases, my players will be 100% fit for any matches even if I take a vacation for a season. Exceptions are injuries, suspensions and exceptional short period between matches of 2 days.
I don't see there will be any difference. If your strategy is keeping less than 22 players, you can always do so.