title: The hidden world of anti-phospholipid antibodies and female infertility: A literature appraisal.
abstract: Even though the association of anti-phospholipid antibodies (aPL) with infertility is debated, infertile women are commonly screened for aPL. To review evidence, a systematic PubMed search was conducted to retrieve papers addressing (i) the association between aPL and infertility, (ii) the positivity rate of criteria and non-criteria aPL in women with infertility, (iii) the association between aPL and assisted reproduction technologies (ART) outcome, (iv) the efficacy of medical treatments on ART outcome, and (v) the effects of ART on thrombotic risk. A total of 46 papers were considered; several limitations emerged: (i) wide heterogeneity in study populations, (ii) non-prospective design in 90% of studies, and (iii) aPL cutoffs not conforming to international guidelines in more than 75% of studies; aPL positivity not confirmed in 89% of studies. Most studies evinced an association between infertility and anti-β2GPI antibodies and almost all non-criteria aPL. The association rate with infertility was below 50% for lupus anti-coagulant, anti-cardiolipin antibodies (aCL), and anti-phosphatidic acid antibodies. According to our estimates, overall positivity rates of criteria and non-criteria aPL tests are 6% and 3% among infertile women, 1% and 2% among controls, respectively. A significant difference in the positivity rate of patients versus controls emerged for aCL only. Five of 18 studies reported a detrimental effect of aPL on ART outcome. Only one of the six studies assessing the effects of treatment on ART outcome among aPL-positive infertile women reported a benefit. All relevant studies reported no increase in the rate of thrombosis among aPL-positive women undergoing ART.
authors.affiliation: Rheumatology Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Experimental Laboratory of Immunology and Rheumatology Researches, Istituto Auxologico Italiano, via Zucchi 18, Cusano Milanino, Milan, Italy.
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Chighizola
authors.affiliation: Department of Obstetrics, Universidade do Estado do Rio de Janeiro, Avenida Professor Manuel de Abreu, 500-1o andar, Vila Isabel CEP, 20550-170, Rio de Janeiro, Brazil; Department of Obstetrics, Instituto Fernandes Figueira, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Guilherme R
authors.initials: GR
authors.lastname: de Jesus
authors.affiliation: Department of Obstetrics and Gynecology, University of Utah Health Sciences, Intermountain Healthcare, 50 N Medical Dr, Salt Lake City, UT 84132, USA. Electronic address: ware.branch@hsc.utah.edu.
authors.forename: D Ware
authors.initials: DW
authors.lastname: Branch
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000175:diagnosis / Q000628:therapy; D011446:Prospective Studies
chemical_list: D017152:Antibodies, Antiphospholipid
keywords: Anti-phospholipid antibodies; Assisted reproduction technologies; Association; Infertility; Positivity rate; Treatment