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