A spokeswoman for the pop star has confirmed that Dion's pregnancy - which she announced in August - has failed.
The couple had its first child with the help of fertility treatments, she became pregnant again with the help of the same technology, and the couple has kept trying despite the latest setback.
Dion tried fertility treatment last month, but that didn't work, and she will make another attempt at getting pregnant this weekend in New York.
Dion's husband Rene Angelil has told a newspaper that he and Dion are disappointed but determined, and that they take comfort in the fact they already have one child.
Dion, 41, and Angelil 67, have an eight-year-old son Rene-Charles.
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