When you create and save a layout, you should be able to use it time and again on other documents of the same structure.
Occasionally, you might find that your layout is suddenly not where it's supposed to be.
The DPI settings for layouts use a fixed coordinate system and, once in awhile, these may become jumbled, which causes the layout to leave it's intended positioning.
Rest assured, there is nothing wrong with your layout and you do not need to recreate it, however, reinstalling your PDF2XL program is the best solution for fixing the problem.
While PDF2XL versions 6.5 and higher automatically save layouts in a repository that it relaunches when reinstalling, you might want to export your saved layouts to a folder on your computer, just to ensure they aren't lost.