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Review
. 2025 Jul 30;24(1):e12670.
doi: 10.1002/rmb2.12670. eCollection 2025 Jan-Dec.

A Systematic Evidence-Based Review Regarding miRNA Polymorphisms in Recurrent Implantation Failure

Bogdan Doroftei  1   2   3 , Ovidiu-Dumitru Ilie  1 , Ana-Maria Dabuleanu  1   2   3 , Mara Doroftei  4 , Ciprian Ilea  1   2 , Sergiu Timofeiov  5   6 , Anca Bivoleanu  2 , Elena Tataranu  7
Affiliations
Review

A Systematic Evidence-Based Review Regarding miRNA Polymorphisms in Recurrent Implantation Failure

Bogdan Doroftei et al. Reprod Med Biol. .

Abstract

Background: This systematic review aimed to evaluate whether specific single nucleotide polymorphisms (SNPs) in miRNAs are associated with recurrent implantation failure (RIF).

Methods: A comprehensive literature search was conducted across PubMed-MEDLINE, Web of Science, Scopus, and the Excerpta Medica DataBASE.

Results: The Newcastle-Ottawa Scale (NOS) yielded an intermediate to high quality, with one study rated with 6 stars, and the remaining four with 7 stars. RIF risk-related genotypes included miR-196a, miR-449b, miR-34a, miR-146aCG+GG-miR-196a2CC, miR-149TT-miR-196a2CC, miR-196a2CC-miR-499AA, miR-608GC-miR-938CC, miR-27aAG-miR-423CC/miR-604AG/GG and miR-34aC>A AA-miR-130aG>A GG. Protective combinations included miR-1302-3, miR-631II-miR-1302-3CT, and miR-938CC-miR-1302-3CT. Protective allele combinations G-T-T-A, C-T, T-T-G, T-T and G-C-A-G, G-A-G, A-G-G were less frequent in RIF cases, whereas A-T-C, T-C-C-T, T-C-T, A-C-G-A, A-A-G-G, G-A-A-A, A-A-C-A and G-G-A haplotypes were more commonly associated with increased risk. Notably, miR-608 GC+CC, miR-1302-3 CC, miR-27a AG+GG, miR-423 CA+AA, miR-604 AG+GG, miR-222 GT+TT, and miR-34a GA+AA were associated with altered coagulation parameters. Additionally, miR-222 correlated with decreased creatinine levels, the G>T mutation with elevated follicle-stimulating hormone (FSH), miR-34aC>A AA genotype with reduced thyroid-stimulating hormone (TSH) levels, and CA+AA with increased blood urea nitrogen (BUN) levels.

Conclusions: This systematic review highlights that specific miRNA SNPs and haplotype combinations are significantly associated with either increased susceptibility to or protection against RIF.

Keywords: allele; coagulation; genotype; hormonal; in vitro fertilization; microRNA; recurrent implantation failure; renal; single nucleotide polymorphism.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA flow diagram of the eligible case–control studies.
FIGURE 2
FIGURE 2
Graphical representation of the overall score following NOS.
See this image and copyright information in PMC

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