Earlier, men's top seed Andy Murray also exited the Rome tournament at the second-round stage.
"I was not playing good a year ago, as well". I think that my movement is not the best, especially on clay.
'I am not feeling so well on this surface'.
The inconsistencies continued for German Angelique Kerber two days after she returned to the top ranking position in the WTA as she suffered a 6-4, 6-0 loss to Anett Kontaveit in the second round of the Rome Masters.
Following Kerber's defeat, the Czech Republic's Karolína Plíšková is now the highest seed in the competition.
Second seed Karolina Plis-kova beat Lauren Davis 6-1 6-1, Madrid victor Simona Halep started with a win over Germany's Laura Siegemund 6-4 6-4 and eighth seed Elina Svitolina put out Alize Cornet 6-4 7-6 (13/11). Elina Svitolina beat Alizé Cornet 6-4 7-6 (11).More news: US governors work Senate as new power brokers in Obamacare repeal
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He beat Great Britain's Kyle Edmund 7-5, 6-4.
Del Potro, the 2009 US Open champion, will face Japan's Kei Nishikori in the last 16.
Rafael Nadal advanced to the third round as fellow Spaniard Nicolas Almagro was forced to quit with a left knee injury.
American veteran Venus Williams proved more reliable with a 6-4 6-3 victory over Lesia Tsurenko of Ukraine.
It is a key preparation event for the French Open, the clay court Grand Slam, due to begin on May 28 at Roland Garros in Paris.