Studies were selected if the prevalence of the abnormal test results for RPL was reported. Only studies which compared women with two pregnancy losses to women with three or more losses were included. Based on current reviews of the literature, the following evidence-based risk-factors for RPL were considered in this review: parental structural chromosomal abnormalities, uterine anomalies, APS, inherited thrombophilia and thyroid disorders. Results of parental chromosomal analysis were considered abnormal if significant rearrangements (e.g. balanced translocations and mosaics) were present. Studies were selected when chromosome analyses were performed with parental peripheral blood lymphocyte cultures. Studies for uterine anomalies were selected if diagnostic testing was performed by hysterosalpingography, hysteroscopy or sonohysterography. Congenital abnormalities (e.g. arcuate uterus, septate uterus, bicornuate uterus and unicornuate uterus) were considered as uterine anomalies.
APS was defined as the presence of thrombosis, pregnancy loss or female morbidity and persistent circulating antiphospholipid antibodies (aPL). aPLs (lupus anticoagulant, IgM anticardiolipin antibodies, IgG anticardiolipin antibodies and beta-2 glycoprotein 1 antibodies) were considered to be present if a test was positive on two occasions >12 weeks apart (Miyakis et al., 2006 (link)).
Inherited thrombophilia was defined in four different sub-categories: Factor V Leiden mutation, prothrombin gene mutation, protein S deficiency and protein C deficiency. Factor V Leiden mutation was considered abnormal if there was a heterozygous or homozygous factor V Leiden G1691A mutation found. Prothrombin gene mutation was defined as heterozygous or homozygous mutations for the G20210A prothrombin (factor II) gene. Functional protein C activity less than 70% and functional protein S activity less than 70% were considered abnormal.
Thyroid disorders were defined as serum levels of thyroid-stimulating hormone (TSH) <0.45 mU/L or TSH >4.5 mU/L with an abnormal free thyroxine level with or without the presence of thyroid peroxidase antibodies.
Studies were excluded when the population examined or the diagnostic methods used were not accurately defined. Only publications in English were considered in our selection.
APS was defined as the presence of thrombosis, pregnancy loss or female morbidity and persistent circulating antiphospholipid antibodies (aPL). aPLs (lupus anticoagulant, IgM anticardiolipin antibodies, IgG anticardiolipin antibodies and beta-2 glycoprotein 1 antibodies) were considered to be present if a test was positive on two occasions >12 weeks apart (Miyakis et al., 2006 (link)).
Inherited thrombophilia was defined in four different sub-categories: Factor V Leiden mutation, prothrombin gene mutation, protein S deficiency and protein C deficiency. Factor V Leiden mutation was considered abnormal if there was a heterozygous or homozygous factor V Leiden G1691A mutation found. Prothrombin gene mutation was defined as heterozygous or homozygous mutations for the G20210A prothrombin (factor II) gene. Functional protein C activity less than 70% and functional protein S activity less than 70% were considered abnormal.
Thyroid disorders were defined as serum levels of thyroid-stimulating hormone (TSH) <0.45 mU/L or TSH >4.5 mU/L with an abnormal free thyroxine level with or without the presence of thyroid peroxidase antibodies.
Studies were excluded when the population examined or the diagnostic methods used were not accurately defined. Only publications in English were considered in our selection.
