Low-Molecular-Weight Heparin for Women With Unexplained Recurrent Pregnancy Loss

Schleußner, E; Kamin, G.; Seliger, G; Rogenhofer, Nina; Ebner, Susanne; Tóth, Bettina; Schenk, Michael; Henes, Melanie; Bohlmann, Michael K.; Fischer, Thorsten; Brosteanu, Oana; Bauersachs, Rupert; Petroff, David

doi:10.7326/m14-2062

Cited by 86 publications

(62 citation statements)

References 35 publications

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“…They concluded that enoxaparin (40 mg once daily) did not improve the chance of a live birth in nonthrombophilic women with unexplained RPL. [14] In another similar multicentre, randomised controlled trial, Schleussner et al [15] determined whether LMWH increases live birth rates in women with unexplained RPL. They enrolled 449 women, with at least 2 early or 1 late miscarriages, at 5 -8 weeks' gestation after confirmation of a viable pregnancy by ultrasonography.…”

Section: Discussionmentioning

confidence: 99%

Preventive role of low-molecular-weight heparin in unexplained recurrent pregnancy loss

et al. 2017

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RESEARCHBackground. Recurrent pregnancy loss (RPL) is a source of great distress for couples, and the search continues for an intervention to improve live birth rates in affected women. A daily injection of low-molecular-weight heparin (LMWH) is often prescribed to women with unexplained RPL, although evidence suggesting a benefit is limited. Objective. To compare the efficacy of LMWH with a placebo in terms of live birth rates in women with unexplained RPL. Methods. All pregnant females between 18 and 44 years of age who reported at the unit of obstetrics and gynaecology, Shifa International Hospital, Islamabad, during April 2013 to January 2014, who had a history of ≥2 consecutive first trimester pregnancy losses were enrolled. All participants were randomly allocated to one of two groups. Group A received a daily dose of 40 mg enoxaparin (LMWH) subcutaneously and group B women received a placebo in the form of multivitamin tablets. Efficacy was defined in terms of live births after the age of viability (i.e. 24 weeks' gestation) and was compared in both treatment and control groups. Risk estimation was also performed and relative risk (RR) along with 95% confidence interval (CI) was calculated. Results. The groups were similar in terms of mean age, gestational age and body mass index. Our results showed no statistically significant difference in live birth rates between the two groups, with 78.8% and 73.8% for group A and B, respectively (p=0.0574). A RR of 1.07 (95% CI 0.9 -1.3) was calculated for group A. Conclusion. Subcutaneous enoxaparin in a once daily dose of 40 mg did not improve the chance of live births in nonthrombophilic women with unexplained RPL when compared with the placebo. Recurrent pregnancy loss (RPL) is one of the commonly encountered complications in reproductive medicine, as the aetiology is often unknown and there are few evidence-based diagnostic and treatment strategies available. There are varying definitions of RPL reported that include ≥2 failed clinical pregnancies as documented by ultrasonography or histopathological examination; [1] or 3 consecutive pregnancy losses, which are not required to be intrauterine. [2] The definition of RPL also includes non-visualised pregnancy losses (biochemical pregnancy losses and/or pregnancies of unknown location) as they have the same negative impact on future live birth rate as intrauterine pregnancy losses. [3] The European Society of Human Reproduction and Embryology released a 2014 consensus statement proposing that RPL describes repeated pregnancy loss regardless of anatomic location. They did not recommend the number of losses required for the problem to be defined as recurrent. However, the statement advised researchers and clinicians to clearly describe the type of pregnancy loss, gestational age, number of prior pregnancy losses and relevant details of ultrasound measurements. [4] There is a consensus that healthy women should not undergo extensive evaluation after a single first trimester or early second trimester spontaneous miscar...

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Section: Discussionmentioning

confidence: 99%

Preventive role of low-molecular-weight heparin in unexplained recurrent pregnancy loss

et al. 2017

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“…For example, some advocated anti-coagulation therapy (such as aspirin or low-molecular-weight-heparin) is effective in improving the pregnancy outcome in women suffered from anti-phospholipid antibody syndrome and RPL but the results were inconsistent among different trials [6, 19–21]. Most of the recently conducted randomized trials failed to show significant benefit of anti-coagulation therapy (either aspirin or low molecular weight heparin alone or if both were combined) to improve the livebirth rates in women with RPL [6, 7, 15]. However, these well-conducted trials actually did not well characterize the underlying possible causative factors in their study subjects, the subgroups due to different etiologies were pooled and no specific analyses were conducted separately on each subgroup.…”

Section: Discussionmentioning

confidence: 99%

“…According to our previous studies, the most common heritable thrombophilias in the thromboembolic patients in Taiwan are protein S and protein C deficiencies [13, 14]. Meanwhile, the selection criteria and treatment protocol varied across different studies and thus we should be cautious when reading reviews based upon meta-analysis [3–5, 15]. …”

Section: Introductionmentioning

confidence: 99%

Low-molecular-weight-heparin can benefit women with recurrent pregnancy loss and sole protein S deficiency: a historical control cohort study from Taiwan

Shen

Cheng

et al. 2016

Thrombosis J

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BackgroundHeritable thrombophilias are assumed important etiologies for recurrent pregnancy loss. Unlike in the Caucasian populations, protein S and protein C deficiencies, instead of Factor V Lieden and Prothrombin mutations, are relatively common in the Han Chinese population. In this study we aimed to investigate the therapeutic effect of low molecular weight heparin upon women with recurrent pregnancy loss and documented protein S deficiency.MethodsDuring 2011–2016, 68 women with recurrent pregnancy loss (RPL) and protein S deficiency (both the free antigen and function of protein S were reduced) were initially enrolled. All the women must have experienced at least three recurrent miscarriages. After excluding those carrying balanced translocation, medical condition such as diabetes mellitus, chronic hypertension, and autoimmune disorders (including systemic lupus erythematosus and anti-phospholipid syndrome), coexisting thrombophilias other than persistent protein S deficiency (including transient low protein S level, protein C deficiency, and antithrombin III), only 51 women with RPL and sole protein S deficiency were enrolled. Initially they were prescribed low dose Aspirin (ASA: 100 mg/day) and unfortunately there were still 39 women ended up again with early pregnancy loss (12 livebirths were achieved though). Low-molecular-weight-heparin (LMWH) was given for the 39 women in a dose of 1 mg/Kg every 12 h from the day when the next clinical pregnancy was confirmed to the timing at least 24 h before delivery. The perinatal outcomes were assessed.ResultsOf 50 treatment subjects performed for the 39 women (i.e. 11 women enrolled twice for two pregnancies), 46 singletons and one twin achieved livebirths. The successful live-birth rate in the whole series was 94 % (47/50). Nineteen livebirths delivered vaginally whereas 28 delivered by cesarean section. The cesarean delivery rate is thus 59.57 %. Emergent deliveries occurred in 3 but no postpartum hemorrhage had been noted.ConclusionsOur pilot study in Taiwan, an East Asian population, indicated anti-coagulation therapy is of benefit to women with recurrent pregnancy loss who had documented sole protein S deficiency.Trial registration ISRCTN64574169. Retrospectively registered 29 Jun 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s12959-016-0118-9) contains supplementary material, which is available to authorized users.

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“…In fact, its prescription has been increasing more and more since the mid-90s and has been shown to be safe for both mother and foetus, in spite of the passage through placenta. In women suffering from early pregnancy loss, it has been shown to be not efficacious [69][70][71][72]. The EAGer doubleblind, placebo-controlled randomised controlled trial (RCT) recently suggested that also preconception-initiated low-dose aspirin did not significantly improve the likelihood of delivering a live born child in 1078 women with one to two previous pregnancy losses.…”

Section: Interventions In Gvcsmentioning

confidence: 99%

Aspirin and heparin in pregnancy

Villani

Tiscia

2015

Expert Opinion on Pharmacotherapy

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Low-Molecular-Weight Heparin for Women With Unexplained Recurrent Pregnancy Loss

Abstract: Pfizer Pharma.

Cited by 86 publications

References 35 publications

Preventive role of low-molecular-weight heparin in unexplained recurrent pregnancy loss

Preventive role of low-molecular-weight heparin in unexplained recurrent pregnancy loss

Low-molecular-weight-heparin can benefit women with recurrent pregnancy loss and sole protein S deficiency: a historical control cohort study from Taiwan

Aspirin and heparin in pregnancy

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