After enduring one fertility setback after another, including a miscarriage in 2010 and Giuliana's bout with breast cancer in 2011, which was discovered while she underwent in vitro treatments, "These last few years have been tough," Giuliana, 39, tells PEOPLE in this week's issue.
A break in the clouds came when they welcomed son Duke via their surrogate Delphine in August 2012. And in January, when they learned Delphine was pregnant with their second child, "Things were finally looking up," the E! News host says. "Duke is our life. I was so excited to give him a sibling."
Sadly, the Rancics revealed to PEOPLE that Delphine miscarried in April, nine weeks into her pregnancy. "It was just heartbreaking," says Giuliana, "I just started sobbing uncontrollably. But I had to get myself together for her. She's really strong and amazing."
The Rancics now face the reality that their next pregnancy try is likely their last chance. "We have one embryo left," she says of the embryos the couple had frozen. "I'm on cancer medication for a few more years. I've had to come to terms with the fact that I may never carry a child. With that said, this next embryo, there's no guarantees. In that case, that's it."
But despite the risk, the two are optimistic. "We're fighters," says Bill. "Duke was a gift after a miscarriage. Delphine will be on board for one more try, so we're certainly optimistic about the future and hope that we’re going to be able to give him a little brother or sister."
For more on the Rancics' story, pick up this week's issue of PEOPLE, on newsstands Friday