What are the most common causes of miscarriage?

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Last updated: November 2, 2026 • View editorial policy

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Causes of Miscarriage

Chromosomal abnormalities are the primary cause of miscarriage, accounting for approximately 60% of cases, with trisomy (particularly trisomy 16) and monosomy X being the most common specific abnormalities 1, 2.

Primary Etiologic Categories

Chromosomal Abnormalities (60% of cases)

The most recent high-quality genomic studies using SNP arrays and chromosomal microarray analysis demonstrate that:

  • Trisomy is the leading chromosomal cause, affecting nearly every chromosome but most commonly chromosome 16 1, 2
  • Monosomy X is the second most common chromosomal abnormality 1, 2
  • Triploidy accounts for a smaller proportion of chromosomal losses 1
  • Copy number variations (CNVs) and structural chromosomal abnormalities, particularly in 8p23 and Xp22 regions, contribute to miscarriage 1

The detection rate of chromosomal abnormalities peaks between 8-10 weeks of gestation 2. Importantly, conventional cytogenetic analysis can only be performed on fresh tissue, making it critical to consider genetic testing at the time of miscarriage 3.

Non-Chromosomal Genetic Causes

For the remaining 40% of miscarriages with normal chromosomal analysis, whole-exome sequencing reveals:

  • Single gene mutations account for approximately 26% of recurrent pregnancy losses with normal chromosomal studies 2
  • Genes involved in oocyte maturation (such as MOS) and other developmental pathways may be implicated 2

Diminished Ovarian Reserve

Women with diminished ovarian reserve (low AMH or elevated FSH) have a significantly higher risk of miscarriage, particularly recurrent pregnancy loss 4. The mechanism appears related to:

  • Higher rates of aneuploid embryos in women with compromised ovarian reserve parameters 4
  • This association persists even in women under 35 years of age 4

However, this relationship remains somewhat controversial, as some studies show that ovarian reserve markers don't affect live birth rates within age categories 4.

Endocrine Dysfunction

Hormonal imbalances represent a major treatable cause of pregnancy loss 5:

  • Thyroid disorders (both hypo- and hyperthyroidism)
  • Polycystic ovary syndrome (PCOS) with insulin resistance
  • Luteal phase defects with inadequate progesterone
  • Poorly controlled diabetes mellitus
  • Hyperprolactinemia

These conditions interfere with implantation, placental development, and maternal-fetal balance 5.

Metabolic Disorders

Abnormalities in four major metabolic pathways contribute to miscarriage 6:

  • Glucose metabolism dysregulation
  • Lipid metabolism abnormalities
  • Amino acid metabolism disorders
  • Oxidative-reduction imbalance

Genes involved in hemostasis regulation and immune pathways (particularly Toll-like receptor signaling) are enriched among CNV-associated genes in miscarriage cases 2.

Age-Related Risk Pattern

Maternal age shows a U-shaped relationship with chromosomal abnormality risk, with the lowest risk at ages 28-29 years 2. Critically, risk begins increasing after age 30—not the conventional threshold of 35 years. Women aged ≥35 years have a 1.72-fold increased risk of chromosomal abnormalities (OR=1.72,95% CI: 1.31-2.26) 2.

Clinical Pitfalls

  • 50% of miscarriages remain unexplained even after comprehensive evaluation 6, 3
  • Chromosomal analysis must be ordered on fresh tissue at the time of miscarriage; delayed testing is not possible with conventional cytogenetics 3
  • Gestational age ≥12 weeks has a protective effect against chromosomal abnormalities (OR=0.27), meaning earlier losses are more likely chromosomal 2
  • For recurrent pregnancy loss with normal chromosomal studies, consider whole-exome sequencing to identify single-gene mutations 2

Diagnostic Algorithm

  1. First-line: Chromosomal microarray analysis on products of conception (detects 60% of causes) 1, 2
  2. For recurrent loss with normal CMA: Whole-exome sequencing (diagnostic yield 26%) 2
  3. Maternal evaluation: Ovarian reserve testing (AMH, FSH), thyroid function, glucose/insulin metabolism, prolactin 4, 5
  4. Pathological examination: Rules out rare disorders with highest recurrence risk 3

The combination of CMA and WES provides complementary diagnostic value and significantly improves the genetic diagnosis rate 2.

References

3
Research

First trimester miscarriage evaluation.

Seminars in reproductive medicine, 2011

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