Two points here:
1. Generally, you don't want to pair a layup with an equivalent orthotropic material. The equivalent orthotropic material already has the information for a full layup contained within. In addition, the thickness of the equiv ortho material, when treated as a ply in a layup is the same as the layup from which the material came. Therefore, if you pair up the layup with the equivalent ortho, you are sort of double bookkeeping.
See the Material Manager user's manual, especially examples 3 and 4, to see how to use equivalent orthotropics and their relationship with layups and laminates.
2. To optimize with discrete layups, the only option is to create many layups or laminates (or use the layups shipped with HyperSizer), put all of these layups into a sizing variable (say the facesheet), and then let HyperSizer select which layup to use.
Equivalent Orthotropic optimization is designed to get you in the ballpark for the relative number of plies that you need and the % of 0s, 45s, 90s. Once you get in the ballpark using equivalent orthos (i.e. take the optimized thickness of the equivalent ortho and divide by the discrete ply thickness to get the number of plies) , then you should create or pick layups from the database that fit these general guidelines and let HyperSizer pick the best layup.