Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
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.

PubMed Disclaimer

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

References

    1. Graham M. E., Jelin A., A. H. Hoon, Jr. , Wilms Floet A. M., Levey E., and Graham E. M., “Assisted Reproductive Technology: Short‐ and Long‐Term Outcomes,” Developmental Medicine and Child Neurology 65 (2023): 38–49, 10.1111/dmcn.15332. - DOI - PMC - PubMed
    1. Adamson G. D., Zegers‐Hochschild F., and Dyer S., “Global Fertility Care With Assisted Reproductive Technology,” Fertility and Sterility 120 (2023): 473–482, 10.1016/j.fertnstert.2023.01.013. - DOI - PubMed
    1. ESHRE Working Group on Recurrent Implantation Failure , Cimadomo D., de los Santos M. J., et al., “ESHRE Good Practice Recommendations on Recurrent Implantation Failure,” Human Reproduction Open 2023 (2023): hoad023, 10.1093/hropen/hoad023. - DOI - PMC - PubMed
    1. Pirtea P., Cedars M. I., Devine K., et al., “Recurrent Implantation Failure: Reality or a Statistical Mirage?: Consensus Statement From the July 1, 2022 Lugano Workshop on Recurrent Implantation Failure,” Fertility and Sterility 120 (2023): 45–59, 10.1016/j.fertnstert.2023.02.014. - DOI - PubMed
    1. Coughlan C., Ledger W., Wang Q., et al., “Recurrent Implantation Failure: Definition and Management,” Reproductive Biomedicine Online 28 (2014): 14–38, 10.1016/j.rbmo.2013.08.011. - DOI - PubMed

LinkOut - more resources