Giuliana Rancic says a surrogate carrying the E! News host's third and last embryo has miscarried, dashing Rancic and her husband's hopes for a second biological child.

"It was painful," Rancic, 40, told People magazine. "We were so optimistic with this last embryo," she said of herself and Bill Rancic, 43. "We thought, 'This is definitely going to work. This is our last shot.' "

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The couple, who starred in the E! reality show "Giuliana & Bill" for seven seasons, learned of the miscarriage on New Year's Eve, about nine weeks after implantation. The Rancics previously had two embryos implanted simultaneously in their surrogate, but the woman suffered a miscarriage in June. Giuliana Rancic told People the latest loss was "the toughest blow. . . . It was a really hard time."

The Rancics' son, Edward Duke, now 2 1/2, had been born via such gestational surrogacy, which differs from traditional surrogacy because a fertilized egg (an embryo) from the parents is implanted into the surrogate, rather than inseminating the surrogate with the father's or another donor's sperm. A gestational carrier brings the baby to term but is genetically unrelated to the child.

Pregnancy would be a risk for Giuliana Rancic due to her regimen of cancer-suppressing medication, following her early-stage breast cancer diagnosis and double mastectomy in 2011. Before that she revealed she had suffered a miscarriage herself in 2010.

Adoption, however, is a possibility, she told the magazine. "We're open to everything," she said. "I think adoption is a beautiful gift you're giving each other."

Rancic, whose memoir "Going Off Script" comes out Tuesday, also addressed public concern over her extreme thinness. She told People she finds it difficult to look at herself in a mirror, and assured she had no eating disorder, saying that her cancer medications affect her metabolism and prevent her from gaining weight.