Serena and Venus Williams were ousted by Ekaterina Makarova and Elena Vesnina in the quarter-finals of the U.S. Open women's doubles in Flushing Meadows, New York on Tuesday.

The fourth-seeded team of Makarova and Vesnina got the better of the Williams sisters as they took advantage of the unforced errors to march their way into the semi-finals 7(7)-6(5) 6-4.

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The demanding schedule of playing both doubles and singles seemed to have taken its toll on the world No. 1 player, Serena, as she called for medical timeout complaining of a problem in her right foot.

After the timeout, Serena went to serve but double-faulted to give the match to the Makarova-Vesnina team.

The Williams sisters have accumulated 13 Grand Slam titles. Their last crown was at Wimbledon in 2012 where they defeated Andrea Hlavackova and Lucie Hradecka who are the defending champions of the tournament.

The Russian team of Makarova and Vesnina on the other hand won the French Open doubles in 2013. They went to the finals at the Australian Open earlier this year but lost to champions Sara Errani and Robert Vinci.

They will face the winners of the Andrea Hlavackova-Jie Zheng team and Kimiko Date-Krumm-Barbora Zahlavova-Strycova duo.

Martina Hingis and Flavia Pennetta also made it to the semi-finals as they toppled fifth seeds Kveta Peschke and Katarina Srebotnik in straight sets 6-4 6-3.

This is their best performance so far after teaming up at Wimbledon and exiting early in the first round. They will go up against the third-seeded team of Cara Black and Sania Mirza who won their match against Zarina Diyas and Xu Yifan also on Tuesday.

Now that the Williams sisters have been eliminated in the tournament, only two players are still alive in both doubles and singles play - Pennetta who is scheduled to play against Serena Wednesday and Makarova who will also play Wednesday against Victoria Azarenka.

Tagsserena williams, Venus Williams, Flavia Pennetta, Cara Black