Anticoagulant therapy in RPL

1. Anticoagulant therapy in RPL Dr. Z. Heidar Assistant professor SBMU

2. The association between recurrent pregnancy loss and APS is based on observational studies, which consistently report that aPL are detected in a higher proportion of women with recurrent pregnancy loss than in controls (up to 20 percent versus <5 percent) antiphospholipid syndrome

3. suggest combined therapy with low-dose ASA (50 to 100 mg per day), beginning when conception is attempted, and prophylactic dose LMWH upon confirmation of intrauterine pregnancy; low-dose ASA and prophylactic or intermediate-dose unfractionated heparin is a reasonable alternative • In three meta-analyses of randomized trials in women with APS, compared with ASA alone, the combination of heparin and ASA significantly reduced pregnancy loss

4. A multicenter, randomized pilot study including 16 women with well-documented antiphospholipid syndrome (APS) reported that treatment with IVIG did not significantly improve the rates of complications. • A study including 40 women compared the efficacy of the combination of low-dose ASA and low molecular weight heparin (LMWH) with use of IVIG for the prevention of recurrent fetal loss The percentage of live births was greater in the LMWH and low-dose ASA group than the IVIG group . APS

5. For women with laboratory criteria for aPL and ≥1 fetal losses ≥10 weeks of gestation or ≥3 unexplained, consecutive, spontaneous pregnancy losses <10 weeks of gestation, we suggest combined therapy with low-dose ASA (50 to 100 mg per day) prophylactic dose LMWH rather than low-dose ASA alone . We continue the regimen for 6 weeks postpartum

6. Immunotherapy — Systematic reviews have consistently found no beneficial effect of immunotherapy for treatment of RPL • A systematic review of 20 trials of high quality showed that immunotherapy did not result in a statistically significant improvement in live births compared to untreated controls Four types of immunotherapy were evaluated Immunotherapy

7. paternal cell immunization • donor cell immunization • trophoblast membrane infusion • intravenous immune globulin(OR 0.98, 95% CI 0.61-1.58; eight studies including 303 participants). • Immune therapy of RPL should be considered experimental, and used only in the setting of a clinical trial regulated by an Institutional Review Board

8. this study was to assess the efficacy of a • high dose intravenous immunoglobulin (HIVIg) therapy, in which 20 g of intact type immunoglobulin was infused daily for 5 • days during early gestation, for women who had a history of four or more consecutive spontaneous abortions of unexplained etiology The live birth rate was 73.3% (44/60). • ISRN Obstetrics and Gynecology 2012 High dose IVIg

9. THROMBOPHILIA — Anticoagulation of women with certain inherited thrombophilias may improve maternal outcome (eg, prevention of venous thromboembolism), but does not appear to prevent pregnancy loss

10. A 2014 Cochrane review including nine trials (n = 1228 women) concluded there was no evidence of an increased frequency of live birth among women with unexplained recurrent miscarriage and inherited thrombophilia treated with anticoagulants (aspirin, heparin, LMWH or combinations of these drugs) inherited thrombophilia

11. Hyperhomocysteinemia :combined anticoagulant therapy with aspirin and LMWH seem to confer added benefit to those with Hhcy phenotypes. PLOS ONE September 2013

12. A large randomized trial found that neither aspirin alone nor aspirin plus heparin improved the live-birth rate of women with unexplained RPL . In this trial, 364 women with unexplained RPL after a thorough evaluation were randomly assigned to receive daily aspirin (80 mg), aspirin plus nadroparin , or placebo. Among the 299 women who became pregnant, the live-birth rates for combination therapy, aspirin alone, and placebo were not significantly different: 69, 62, and 67 percent, respectively. Aspirin with or without heparin in unex. RPL

13. Similarly, another trial randomly assigned 294 women with≥2 consecutive unexplained pregnancy losses at ≤24 weeks to treatment with enoxaparin and low dose aspirin or no treatment. Medical therapy did not reduce the rate of pregnancy loss, which was 22 percent with drug treatment and 20 percent without it

14. Neither aspirin combined with nadroparin nor aspirin alone improved the live-birthrate, as compared with placebo, among women with unexplained recurrent miscarriage. • nejm.org april 29, 2010 Unexplained RPL

15. 520 women with unexplained recurrent miscarriage were assigned to receive aspirin (80 mg daily) for two month before pregnancy and after confirmation of a viable pregnancy until 36 weeks of gestation or receive aspirin, as the same, plus heparin (5000 unit twice a day) subcutaneously after confirmation of viable pregnancy until 4 weeks after delivery • There was not any significantly difference • Iranian Journal of Reproductive Medicine Vol. 12. No. 1. pp: 73-76, January 2014 Unexplained RPL

16. In a large RCT in which IVIG was evaluated in women with idiopathic secondary recurrent miscarriage; no treatment benefit was found. The meta-analysis results with two prior RCTs, also showed no significant effect of treatment with IVIG • Hum Reprod. Sep 2010

17. overall live birth rates after normal and abnormal diagnostic evaluations for RPL are 77 and 71 percent respectively • ANTIPHOSPHOLIPID SYNDROME — Drugs such as aspirin and heparin appear to improve pregnancy outcome in women with antiphospholipid syndrome who have recurrent fetal losses.