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Giuliana Rancic

Steve Granitz/WireImage

Giuliana Rancic and her husband, Bill Rancic, have always been open about their struggles with fertility, but now the E! News co-anchor reveals to People magazine that they have lost their final embryo.

Although they already have son Duke, Giuliana and Bill were hoping to give their firstborn a sibling, something that just became that much harder due to their tragic loss. The couple learned on New Year's Eve that their surrogate, who was pregnant with their third and final embryo—had miscarried.

"It was painful," Rancic, 40, tells People. "We were so optimistic with this last embryo. We thought, 'This is definitely going to work. This is our last shot.'"

After a surrogate gave birth to Duke in 2012, the couple had three embryos left and successfully implanted two into their surrogate. Sadly, she miscarried only weeks later, but the reality TV couple remained hopeful because they still had one more chance. But their latest lost, she tells the magazine, "was the toughest blow."

She adds, "It was a really hard time."

Getting pregnant herself would prove risky for the E! star after being diagnosed with breast cancer in 2011. After undergoing a double mastectomy soon after, Giuliana began—and still takes—a cancer-suppressing medication that makes it hard for her to gain weight.

But now with pregnancy becoming something harder than ever, Giuliana says she and her hubby are open to any and all options available to them, including adoption. "We're open to everything," she says. "I think adoption is a beautiful gift you're giving each other. And it's funny, I'm even more open to [adoption] than I was before. Because I think to myself, 'I love Duke so much, if I couldn't take care of him, I hope there would be someone else who would love him.'"

Even if they don't have another child, Giuliana has said that she is blessed to have her family as is. "I have to remind myself that I'm very fortunate to have what I have," she previously told People.

"It's really about knowing there's a bigger plan at play, so for some reason, it wasn't meant to happen this way," she added. "It'll all be clear one day soon."