This is the second time that Mayer's had to juggle important personal and professional news.
When she initially accepted the top job at Yahoo in July 2012, Mayer was in her third trimester.
After giving birth to her son that September, she sparked further controversy by taking only a few weeks of maternity leave.
That put Mayer's private decision at the center of a very public debate.
Many working women were critical of Mayer's decision, saying that it set an unreasonable example for women recovering from childbirth. Others said that it was Mayer's choice to do what she thought was best for her personal life and the good of the company.
This time around, Mayer's in a trickier professional position.
When she gave birth to her son, Yahoo investors and analysts viewed Mayer as a potential savior for Yahoo. The former Googler was seen as having the right kind of energy to turn around a 20-year-old company that had floundered under a line of chief executives with different visions for Yahoo's future.
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More than three years later, company watchers are saying that Mayer's nearly out of time to prove her leadership can right the ship, echoing the concerns from the activist investors who scuttled her original plans to revive Yahoo.
After Wednesday's announcement about the possibility of a spin-off of Yahoo's core business - a move that many think could lead to a sale down the line - analysts were quick to say that Mayer has a year, at most, to restoke the fires in Sunnyvale, Calif.
With Yahoo again at a crucial transition point, Mayer has said that she will take "limited leave" following the birth of her daughters and will again work throughout her time outside the office.
In other words, while she'll be on leave, there's unlikely to be much rest.