If your binding method or finishing requires a special type of fold that your printers' folding machine can't handle, hand-folding is necessary and adds to the cost. Talk to your printer about what types of standard folds they can handle and design accordingly to take advantage of those standard folds. Different printers may offer different standard folds depending on their equipment. Find out in advance. You may consider changing printers or outsourcing the finishing to take advantage of a greater variety of standard folds and less expensive machine folding options.
More ways to Design With Printing in Mind that can save time and money.