However, it's only made their bond stronger.
"The challenging times will bring you closer together in marriage," Bill said on E! News.
Bill, 43, and Giuliana, 39, welcomed their son Duke via surrogate in 2012, and have been hoping to give him a sibling soon. At the time of the miscarriage, their surrogate, Delphine, was nine weeks pregnant.
"Before we had Duke we had struggles there too. We were trying for years to have a baby. We had a miscarriage then," Giuliana said. "To see Duke, you realize, wow, everything is meant to happen for a reason. We wouldn't have Duke. It's pretty incredible to think how life works."
Her husband added that every couple goes through highs and lows in marriage and "you have to battle things out."
"For us, we're not quitters," he added. "We're gonna hopefully have another baby one day soon."