April 01, 2015 10:00 AM

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Giuliana Rancic finally speaks out about her Fashion Police controversy, the health problems she’s kept secret, and why she’s become shockingly thin. Subscribe now for instant access to the exclusive interview, only in PEOPLE.

Her struggle with infertility was chronicled on Giuliana Rancic‘s reality show, and now, the E! News host is sharing another devastating personal blow.

Giuliana and her husband Bill, who welcomed son Duke via surrogate in 2012, learned on New Year’s Eve that their surrogate — who was pregnant with their third and last remaining embryo — had miscarried.

“It was painful,” Giuliana, 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 Duke, now 2½, was born, the Rancics had three remaining embryos. Two were successfully implanted in their surrogate in 2014; she miscarried weeks later. The latest loss, however, “was the toughest blow,” Giuliana says. “It was a really hard time.”

Getting pregnant herself would be a risk for the reality star, who is taking cancer-suppressing medication following her 2011 breast cancer diagnosis (and subsequent double mastectomy), but Giuliana remains hopeful about growing her family.

“We’re open to everything,” says the E! personality, whose memoir, Going Off Script, hits shelves April 7. “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.’ ”

For much more from Rancic, including a very personal reveal and the truth about the Fashion Police controversy, pick up the latest issue of PEOPLE, on newsstands Friday

— Aili Nahas

RELATED: Giuliana Rancic: I Know I’m Too Thin

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