For what reason the checkbox "Do not include last upsells" is used?
If the same customer makes several orders in your web store during some period of time and several e-mails with Offers are sent to him, then by marking the checkbox Do not include last upsells, you thereby will exclude the reiteration of those upsells (suggested products), which have already been sent to customer on the previous emails. Thus, each time you can propose new additional products to your customers making several orders and thereby increase the conversion of additional sales.