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.

Keywords

Antiphospholipid syndrome antiphospholipid antibodies pregnancy loss abortion aspirin heparin

Get full access to this article

View all access options for this article.

References

Galarza-Maldonado

Kourilovitch

Pérez-Fernández

. Obstetric antiphospholipid syndrome. Autoimmun Rev 2012; 11: 288–295.

Matsubayashi

Sugi

Arai

. Different antiphospholipid antibody specificities are found in association with early repeated pregnancy loss versus recurrent IVF-failure patients. Am J Reprod Immunol 2001; 46: 323–329.

Zammiti

Mtiraoui

Hidar

Fekih

Almawi

Mahjoub

. Antibodies to beta2-glycoprotein I and annexin V in women with early and late idiopathic recurrent spontaneous abortions. Arch Gynecol Obstet 2006; 274: 261–265.

Miyakis

Lockshin

Atsumi

. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306.

Mtiraoui

Zammiti

Fekih

Hider

Almawi

Mahjoub

. Lupus anticoagulant and antibodies to beta 2-glycoprotein I, annexin V, and cardiolipin as a cause of recurrent spontaneous abortion. Fertil Steril 2007; 88: 1458–1461.

Alijotas-Reig

Ferrer-Oliveras

Rodrigo-Anoro

Farran-Codina

Cabero-Roura

Vilardell-Tarres

. Anti-beta(2)-glycoprotein-I and anti-phosphatidylserine antibodies in women with spontaneous pregnancy loss. Fertil Steril 2010; 93: 2330–2336.

Lee

Branch

Silver

. Immunoglobulin A anti-beta2-glycoprotein antibodies in women who experience unexplained recurrent spontaneous abortion and unexplained fetal death. Am J Obstet Gynecol 2001; 185: 748–753.

Lee

Emlen

Scott

Branch

Silver

. Anti-beta2-glycoprotein I antibodies in women with recurrent spontaneous abortion, unexplained fetal death, and antiphospholipid syndrome. Am J Obstet Gynecol 1999; 181: 642–648.

Pattison

Chamley

Birdsall

Zanderigo

Liddell

McDougall

. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial. Am J Obstet Gynecol 2000; 183: 1008–1012.

10.

Dendrinos

Sakkas

Makrakis

. Low-molecular-weight heparin versus intravenous immunoglobulin for recurrent abortion associated with antiphospholipid antibody syndrome. Int J Gynaecol Obstet 2009; 104: 223–225.