Table 1

Overview of miscarriage-associated factors and their possible causal role for miscarriage/recurrent miscarriage, possible treatments and proposals for future research
Biomarker/lifestyle factor in patients with miscarriage/recurrent miscarriage Documentation for causality Possible treatment and its documented effect Future research
Parental chromosome abnormalities [4,5] Strong PGD: weak Identification of high risk carriers through clinical history; RCT of PGD/no PGD
Autoantibodies [6,7] Moderate Prednisone, IvIg: weak RCTs of prednisone and/or IvIg
NK cell dysfunction [8-10] Weak to moderate Prednisone, IvIg: weak Develop standardized methods of measuring NK cells in the endometrium; establish normal values of NK cells in the blood and endometrium during pregnancy
Abnormal HLA-G expression [11] Weak to moderate Prednisone, IvIg: weak Develop standardized methods for measuring soluble and membrane-bound HLA-G
Hereditary thrombophilia [12,13] Moderate Heparin, LDA: weak RCTs of heparin and LDA
Acquired thrombophilia [12,14] Strong Heparin, LDA: moderate Larger RCTs of heparin and LDA
Thyroid autoimmunity [15-17] Strong Levothyroxine: weak RCTs of levothyroxin
PCOS [18] Weak Weight loss Cohort studies of miscarriage rates subsequent to weight loss vs no weight loss
Sperm DNA fragmentation [19,20] Moderate Sperm separation: no Identify the most specific assays; establish methods for efficient sperm selection.
Disrupted endometrial selection [21-26] Recently proposed mechanism Correction of decidual selective phenotype by hormonal modulators, including progesterone. Intervention studies using hormonal treatments in the early luteal phase are being carried out
Uterine malformations [27,28] Weak to moderate Septal resection RCTs of septal resection/no resection
hCG gene polymorphisms [29,30] Weak to moderate hCG supplementation: weak RCTs of hCG supplementation
Alcohol consumption [31] Moderate Alcohol cessation NA
Obesity [32,33] Weak to moderate Weight loss: weak Cohort studies of miscarriage rates subsequent to weight loss vs no weight loss

hCG human chorionic gonadotropin, HLA human leukocyte antigen, IvIg intravenous immunoglobulin, LDA low-dose aspirin, NK natural killer, PCOS polycystic ovary syndrome, PGD preimplantation genetic diagnosis, RCT randomized controlled trial.

Larsen et al.

Larsen et al. BMC Medicine 2013 11:154   doi:10.1186/1741-7015-11-154

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