1 Classification n APS, n Hereditary Thrombophilias, n Unexplained RPL,

2 Role of Aspirin in RPL n APS, Metaanalysis of 3 RCT (135 patients), (Empson et al, 2002, including :- Cowchock & Reece, 1997; Pattison et al, 2000; Tulppala et al, 1997), RR = 1.05, (CI, ) n Unexplained RPL, 3 RCT’s, (Tulppala, et al 1997, Kaandorp, et al 2010, Visser, et al 2011), RR=0.96 (CI, ) n Hereditary Thrombophilias, 2 RCT’s, (Kaandorp, et al 2010, Visser, et al 2011), RR=0.68 ( CI, ) n In RPL, Aspirin has no beneficial effect

3 Metaanalysis on Heparin & LMWH in APS 0.1 Rai et al, 1.88 ( ) Kutteh et al, 2.45 ( ) Farquharson et al, 1.18 ( ) Overall, 1.65 ( ) 101 n No measurement of  2 GP-1 antibodies n No correction for chromosomal aberrations n No correction for embryonic structural malformations n Overall benefit 22%

4 Heparins in Hereditary Thrombophilias (71.6%)(50.6%) (73.3%)(58.3%) Clark: Heparin & Aspirin vs surveillance alone, Kaandorp: Nandoparin & Aspirin vs Placebo Visser: Enoxaparin & placebo vs Aspirin

5 Anticoagulants in Hereditary Thrombophilia (Carp et al, 2003) 12/176/7 3/12 26/37 12/2622/497/11 8/13 RR=1.87 (95% CI= )

6 Heparins in Unexplained RPL RR (CI)ControlHeparin 0.95 ( )111/140 (79.3%)111/143 (77.6%)Clark, et al 2010* Heparin & Aspirin vs surveillance alone 0.92 ( )42/50 (84.0%)44/54 (81.5%)Carp, et al 2006 Enoxaparin vs Aspirin 0.84 ( )47/81 (58.0%)45/92 (48.9%)Kaandorp, et al 2010 Nandoparin & Aspirin vs Placebo 1.24 ( )34/57 (59.6%)35/51 (68.2%)Visser, et al 2011 Enoxaparin & placebo vs Aspirin n No beneficial effect

7 RCOG Guideline (2012)

8 ASRM Guideline (2012)

9 De Jong et al, 2014 n 9 studies, of 1228 women n Assessed enoxaparin or nadroparin or aspirin or a combination of both n No beneficial effect found n This review does not support the use of anticoagulants in women with unexplained recurrent miscarriage.

10 Role of Aspirin in APS (Empson et al, 2002) PlaceboAspirin 7/8 (87.5%)10/11 (91%)Cowchock & Reece, /20 (85%)16/20 (80%)Pattison et al, /33 (84.9%)26/33 (78.8%)Tulppala et al, /61 (85.2%)52/64 (81.3%)Total Aspirin alone did not significantly reduce pregnancy loss, RR = 1.05, (95% CI, )

11 Preconception Aspirin n Preconception aspirin was not significantly associated with live birth or pregnancy loss in women with 1 – 2 previous losses. n Higher live birth rates in women with a single loss at < 20 weeks during the previous year. n Preconception aspirin is not recommended for decrease pregnancy loss or increase live birth rates.