Key result
The authors argue that observational studies showing large benefits of antithrombotic therapy in recurrent pregnancy loss are likely confounded, as meta-analyses of RCTs show no significant benefit.
Why the study?
Does antithrombotic therapy improve live birth rates in women with recurrent pregnancy loss?
Does antithrombotic therapy improve live birth rates in women with recurrent pregnancy loss?
This editorial letter cautions against using confounded observational data to support antithrombotic therapy in recurrent pregnancy loss, reiterating that high-quality RCTs show no benefit.
Sir, We read with interest the study by Grandone et al. (2021). The authors described the results of a prospective observational cohort study and conclude that in women with recurrent pregnancy loss—especially in women with inherited thrombophilia—antithrombotic therapy may have a role in increasing the chances of live birth. In addition, the authors argue that there is an absence of large randomized controlled trials (RCTs) with inclusion criteria taking into account the most frequent causes of pregnancy loss. We strongly disagree with this statement, which may leave physicians and patients confused and in doubt about the usefulness of antithrombotic treatment for recurrent pregnancy loss. Surprisingly, the authors did not elaborately point to the widely available high-level evidence, i.e. RCTs, in women with unexplained recurrent miscarriage. The benefit of antithrombotic therapy, either unfractionated or low-molecular-weight-heparin (LMWH) with or without aspirin (ASA) in women with unexplained pregnancy loss with or without thrombophilia has been addressed by numerous RCTs. In a systematic Cochrane review (de Jong et al., 2014), 9 studies, including data of 1228 women, were included. Studies were heterogeneous with regard to study design and treatment regimen and three studies were considered to be at high risk of bias. Two of these three studies at high risk of bias showed a benefit of one treatment over the other, but in sensitivity analyses in which studies at high risk of bias were excluded, anticoagulants did not have a beneficial effect on live birth, regardless of which anticoagulant was evaluated: risk ratio (RR) for live birth in women who received LMWH compared to ASA RR 1.08 (95% CI 0.93–1.26, n = 239), and in women who received LMWH and ASA compared to no treatment RR 1.01 (95% CI 0.87–1.16, n = 322). Taken together, there is convincing high-level evidence that in women with unexplained recurrent pregnancy loss there is no benefit of either LMWH or ASA.
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Scheres et al. (2021) conducted a letter in Recurrent pregnancy loss. Antithrombotic therapy (LMWH and/or Aspirin) vs. No treatment was evaluated. The authors argue that observational studies showing large benefits of antithrombotic therapy in recurrent pregnancy loss are likely confounded, as meta-analyses of RCTs show no significant benefit.
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