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Table 1 Overview of miscarriage-associated factors and their possible causal role for miscarriage/recurrent miscarriage, possible treatments and proposals for future research

From: New insights into mechanisms behind miscarriage

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 [810] 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 [1517] 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 [2126] 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
  1. 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.