Recurrent early pregnancy loss and antiphospholipid antibodies: where do we stand?

Abstract

Evidence from basic science studies supports a causative relationship between antiphospholipid antibodies (aPL) and recurrent early miscarriage (REM) (prior to 10 weeks of gestation). However, human studies have not consistently found a relationship between aPL and REM. Members of the Obstetric Task Force of the 14th International Congress on Antiphospholipid Antibodies performed a literature review of the association of aPL and REM and searched for clinical trials in women with REM who tested positive for aPL. Of the 46 studies that investigated the relationship between aPL and REM, 27 found a positive association, seven found no association, and the remaining 12 papers could not report an association (lack of control group). The main identified problems for such conflicting results were varying definitions of REM (two or three abortions, not necessarily consecutive; different gestational age at which pregnancy losses occurred); analysis of patients with previous fetal death (>10 weeks) in the same group of REM; and different definitions of "positive aPL" (cutoffs not following international recommendations; small number of studies confirmed persistence of positive aPL after six to 12 weeks). The 10 identified randomized trials with proposed treatments for women with REM who test positive for aPL also had heterogeneous inclusion criteria, with only one trial limited to subjects who would meet the current criteria for antiphospholipid syndrome (APS) by both clinical and laboratory criteria. Against this background, we conclude that the association between REM and aPL remains inconclusive and that the findings of treatment trials are at best inconsistent and at worst misleading. More convincing data are critically needed. Studies that identify, or at least stratify, according to international consensus criteria and include standardized core laboratory testing results are crucial if we are to establish an evidence-based association between aPL and REM and treatment recommendations.

The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): A survey of 1000 consecutive cases

“…Interestingly, examining poor obstetric outcomes, there is a significant increase of recurrent miscarriages in the presence of category IIb. Moreover, other studies yielded similar results [38], in spite of both different inclusion criteria and positive laboratory aPL results. Otherwise, when we focus on the manifestations related to placental insufficiency, we observed a strong association between different laboratory categories and PE (around 15-20% with categories I and IIa, and 10-15% with categories IIb and IIc).…”

The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): A survey of 247 consecutive cases

“…14). However, other authors argue the contrary [28][29][30]. The differences in results of the commented studies can be partially explained by different inclusion criteria and the definition of positive laboratory aPL results.…”

“…The Registry showed that less than one third of the historical cohort and less than 10% of the latest gestations have suffered foetal loss. This is a well-known aPL-related complication [30]. As previously mentioned, foetal losses were initially thought to be more frequent than early recurrent miscarriages.…”

Hypofibrinogenemia and the α-Fibrinogen Thr312Ala Polymorphism may be Risk Factors for Early Pregnancy Loss

“…A causative relationship between aPLs and recurrent early miscarriage (prior to 10 weeks of gestation) is supported by many studies, 14 and treatment with heparin and low-dose aspirin is associated with favorable pregnancy outcomes. 15 In the current study, UFH therapy was associated with a favorable pregnancy outcome in 34 of 35 cases, including 2 cases who have successfully maintained their pregnancy after UFH treatment.…”