The Western and Southern Open lost its top two women's seeds on Sunday with number one Karolina Pliskova and number two Sofia Kenin crashing out of the U.S. Open tuneup.
Czech Pliskova, who had a first-round bye, slammed down 11 aces but also committed nine double faults in a 7-5 6-4 defeat to Russia's Veronika Kudermetova.
Australian Open champion Kenin also struggled to get going after the Covid-19 layoff, losing 6-1 7-6(7) to France's Alize Cornet, who beat American wildcard Catherine McNally 6-0 6-4 in the opening round, dropping just 10 points in the first set.
"It didn't feel like I had any rhythm," said Kenin. "I don't know why I let that happen.
"I literally couldn't feel the ball, like literally two sets. I don't even know how I came back, to be honest.
"It was really frustrating."
Marketa Vondrousova continued her run of poor form as the Czech 10th seed lost 6-3 6-7(3) 6-4 to German qualifier Laura Siegemund in a first-round clash.
2019 French Open finalist Vondrousova, who also made a first-round exit at the WTA Tour's restart in Palermo, was up a break 4-2 in the third and looking set for victory until Seigemund swept the last four games.
Estonian 12th seed Anett Konaveit, coming off a runner-up finish in Palermo, moved into the second round with a 6-3 6-1 win over Russian lucky loser Daria Kasatkina, while 14th seed Elise Mertens of Belgium thumped Swede Rebecca Peterson 6-0 6-2.
In the men's draw, Greek fourth seed Stefanos Tsitsipas eased to a 6-1 6-3 second-round win over South Africa's Kevin Anderson while seventh seed David Goffin sailed past Croatia's Borna Coric 7-6(6) 6-4 into the third round.
Ninth seed Diego Schwartzman was a 7-6(2) 6-3 first-round winner over Norway's Casper Rudd while 11th seeded Russian Karen Khachanov topped Kazakhstan's Alexander Bublik 6-4 6-4.
Bulgarian 14th seed Grigor Dimitrov disposed of Frenchman Ugo Humbert 6-3 6-4.
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