Top seeds and hot favourites, Sania and Martina went down to the seventh seeded American-Czech pair 5-7 2-6 in the Clay Court Grand Slam.
With this defeat, India's campaign in the main draw of the French Open is over.
It was a below par performance by Sania and Martina, managing to win just a total of 61 points as compared to 70 by their lower-ranked rivals.
Although they fought hard in the opening set, the Indo-Swiss duo could not step up the momentum when needed and lost 5-7.
In the second set, Sania and Martina turned out to be no match to their opponents. They lost their serve in the beginning of the set itself to fall behind 0-2.
Leading 2-0, Mattek-Sands and Safarova tightened the noose and the top seeds were left to play only the catching up game, which they eventually lost to bow out of the tournament.
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