Premier League side West Ham failed to claim a place in the group stage of the Europa League as they were beaten by Romanian champions Astra Giurgiu.
Filipe Teixeira scored the only goal in the second leg of the playoff round at the London Stadium, netting on the stroke of half-time to hand Astra a 1-0 victory for a 2-1 aggregate success.
Sam Byram's crossfield ball gave Reece Burke too much to do and left both Hammers full-backs hopelessly out of position as the former Barnsley and West Brom midfielder scored.
The Hammers crashed to their first defeat at the London Stadium to the same club that knocked them out of Europa League qualifying one round earlier last season.
Italian side Sassuolo completed formalities against Red Star Belgrade, drawing 1-1 away for a 4-1 aggregate win. Domenico Berardi put them ahead before Aleksandar Katai levelled.
St Etienne survived the sending-off of goalkeeper Stephane Ruffier to play out a 0-0 draw with Beitar Jerusalem at the Stade Geoffroy Guichard and go through 2-1 on aggregate.
Shakhtar Donetsk beat Istanbul Basaksehir 2-0 after an own goal from Joseph Attamah and a Marlos penalty to go through 4-1.
Olympiakos needed extra time against Portuguese side Arouca. Gege's 80th-minute strike in Piraeus meant the aggregate score was 1-1 at full time, but Alejandro Dominguez and Brown Ideye -- once of West Brom -- won it for the Greeks.
Panathinaikos were held 1-1 at Brondby, but went through 4-1 overall, while first-half goals from Garry Rodrigues and Giorgos Tzavellas gave PAOK Salonika a 2-0 win over Dinamo Tbilisi and a 5-0 aggregate success.
Fenerbahce completed a straightforward victory over Grasshoppers, winning 2-0 in Zurich for a 5-0 aggregate success with late goals from Fernandao and Miroslav Stoch.
Austria Vienna beat Rosenborg 2-1 away, replicating their first-leg success, with second-half goals from Alexander Grunwald and Olarenwaju Kayode, while AZ Alkmaar's goalless draw with FK Vojvodina ensured they went through 3-0 on aggregate.
Anderlecht completed an emphatic 6-0 aggregate win over Slavia Prague with a second successive 3-0 victory. Penalties from Youri Tielemans and Lukasz Teodorczyk and a further effort from Michael Heylen did the job.
Gent were also in good goal scoring form in Macedonia, beating Shkendija 4-0 for a 6-1 overall victory. Kalifa Coulibaly netted twice, with Jeremy Perbet and Renato Neto also on target.
Goals from Mbwana Samatta and Leon Bailey settled Genk's nerves as they beat Lokomotiva Zagreb 2-0 at home to go through 4-2 on aggregate.
Maccabi Tel Aviv came through on penalties against Hajduk Split after a 3-3 aggregate draw. Two goals from Marko Cosic ensured a 2-1 win on the night for the Croatian side but they were beaten 4-3 in the shootout.
Sparta Prague survived a scare against Danish side Sonderjyske, coming from behind in the Czech capital to prevail 3-2 on the night and aggregate.
After a goalless first leg, Mikael Uhre and Troels Klove put the Danes ahead but Sparta responded through David Lafata and Josef Sural before Jakub Brabec netted the winner five minutes from time.
BATE Borisov were unable to turn around their tie against Astana, being held 2-2 in Belarus to go out 4-2.
Mikhail Gordeichuk gave Borisov early hope of turning around the tie but Nemanja Maksimovic and Patrick Twumasi made sure for the Kazakhstani side before Igor Stasevich scored a late penalty consolation for the hosts, who also had Aleksei Rios sent off.
Azerbaijani side Qarabag overturned a 1-0 first-leg deficit to progress at the expense of Gothenburg. Goals from Rashad Sadygov, Muarem Muarem and Dani Quintana gave them a 3-0 win in Baku.
Jan Sykora scored a hat trick to send Slovan Liberec through with a 3-0 win, 4-0 on aggregate, against AEK Larnaka, who had captain Ander Murillo sent off late on.
Tiago Pinto scored both goals for Turkish side Osmanlispor as their 2-0 win saw off Danish outfit Midtjylland 3-0 overall.
AS Trencin's 2-0 win at Rapid Vienna proved academic as they went out 4-2 on aggregate while NK Maribor's 1-0 defeat of FK Qabala was not enough as they went down 3-2 overall.
FK Krasnodar drew 0-0 at Partizani Tirane to progress courtesy of their 4-0 first-leg win.