Molecular Biomarkers and Pathways in Recurrent Spontaneous Abortion: A Systematic Review
In brief
Chromosomal abnormalities account for nearly half of first-trimester recurrent pregnancy losses
A review of nine studies found chromosomal abnormalities in nearly half of first-trimester recurrent losses, while variants in genes including NLRP7, KHDC3L and VEGF were also linked to risk. These findings offer clues to how pregnancy loss may occur, but the evidence comes largely from small, single-population studies; broader validation is needed before biomarkers can guide routine care.
- Journal
- International journal of fertility & sterility (Q2)
- Published
- 3 October 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Malihe Kamali Moradzadeh, Marzieh Azadian, Neda Shafie, Sajad Alavimanesh, Shayan Khalili Alashti, Zahra Dorri
- PMID
- 42929011
- DOI
- 10.22074/ijfs.2026.2069378.1935
Why clinicians should know about it
- Picked for Genetics (clinical) (top studies of the week, 1 November 2026): Reviews genetic evidence relevant to recurrent pregnancy loss
Abstract
BACKGROUND: Recurrent spontaneous abortion (RSA), defined as the loss of two or more consecutive pregnancies, affects approximately 15-25% of couples and represents a significant clinical and emotional burden in reproductive medicine. Despite advances in maternal and fetal care, a substantial proportion of cases remain idiopathic, emphasizing the need to elucidate underlying biological mechanisms. This systematic review aimed to evaluate genetic and molecular biomarkers associated with RSA and to synthesize their role in its pathogenesis, in order to inform future diagnostic and therapeutic strategies. MATERIALS AND METHODS: This systematic review synthesizes current evidence on genetic and molecular biomarkers associated with spontaneous abortion, based on a systematic search of PubMed, Scopus, Web of Science, EMBASE, and ClinicalTrials.gov (January 2012-June 2024), focusing on findings derived from next-generation sequencing (NGS), array comparative genomic hybridization (aCGH), and bioinformatics approaches; nine eligible studies were included. RESULTS: Chromosomal abnormalities, including aneuploidies and structural rearrangements, account for nearly half of all first-trimester recurrent spontaneous abortions and play a central role in embryonic viability. In addition, specific gene variants and polymorphisms, including NLRP7, KHDC3L, and VEGF [e.g., rs1570360: odds ratio (OR)=1.42, 95% confidence interval (CI): 1.10-1.84; rs3025039], are associated with increased risk of recurrent pregnancy loss through disruption of embryogenesis, immune tolerance, and placental angiogenesis. CONCLUSION: Genetic and non-coding RNA biomarkers offer biologically plausible insights into the mechanisms of RSA, but current evidence remains preliminary and derived mainly from small, single-population studies; multi-ethnic validation and standardized protocols are needed before these markers can be translated into routine clinical practice.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.