REVIEW
Evaluation of Th1-Th2 Balance in Patients With Unexplained Recurrent Spontaneous Abortion: A Systematic Review and Meta-Analysis
Reza Kargar,
Zahra Yahoo,
Hosein Rafiemanesh,
Saeed Aslani,
Atefeh Shamosi,
Hamed Mohammadi,
Reza Kargar
Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorZahra Yahoo
School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorHosein Rafiemanesh
Department of Epidemiology and Biostatistics, School of Public Health, Alborz University of Medical Sciences, Karaj, Iran
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorSaeed Aslani
Department of Molecular and Translational Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia
Search for more papers by this authorAtefeh Shamosi
Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorCorresponding Author
Hamed Mohammadi
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorReza Kargar,
Zahra Yahoo,
Hosein Rafiemanesh,
Saeed Aslani,
Atefeh Shamosi,
Hamed Mohammadi,
Reza Kargar
Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorZahra Yahoo
School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorHosein Rafiemanesh
Department of Epidemiology and Biostatistics, School of Public Health, Alborz University of Medical Sciences, Karaj, Iran
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorSaeed Aslani
Department of Molecular and Translational Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia
Search for more papers by this authorAtefeh Shamosi
Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorCorresponding Author
Hamed Mohammadi
Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran
Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
Search for more papers by this authorFirst published: 12 July 2025
ABSTRACT
Objective
Unexplained recurrent spontaneous abortion (URSA) poses a major challenge in reproductive medicine, with increasing evidence of maternal immune dysregulation. This systematic review and meta-analysis assessed differences in T helper (Th) 1 and Th2 cell frequencies and their ratio between women with URSA and healthy fertile controls.
Methods
A comprehensive search of PubMed, Scopus, and Web of Science (WoS), up to October 2024, included studies evaluating peripheral blood Th subsets by flow cytometry.
Results
Meta-analyses were performed for Th1(IFN-γ), Th1(TNF-α), Th2(IL-4), Th2(IL-10), and Th1/Th2 ratios. Th1(IFN-γ) frequencies were significantly higher in URSA (mean difference [MD] = 2.31, 95% CI = 0.30–4.33, p = 0.02), while Th2(IL-4) levels were lower (MD = −0.51, 95% CI = −0.91 to −0.11, p = 0.01). No significant differences were observed for Th1(TNF-α) (SMD = 0.25, 95% CI = −0.06 to 0.55, p = 0.11) and Th2(IL-10) (SMD = −0.28, 95% CI = −0.62 to 0.05, p = 0.10). The Th1(IFN-γ)/Th2(IL-4) ratio was significantly elevated (MD = 5.37, 95% CI = 1.47–9.27, p = 0.007), reflecting a shift toward a Th1-dominant immune profile.
Conclusions
These findings support the role of Th1/Th2 imbalance in URSA and suggest its potential value as a diagnostic or prognostic marker.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| aji70125-sup-0001-figureS1.jpeg1.1 MB | Supporting Fig 1: Forest plot presenting analyses based on SMD for (A) Th1(IFN-γ) and (B) Th2(IL-4) without Ng's study. |
| aji70125-sup-0002-tableS1.docx13.5 KB | Supporting Table 1: Syntax in each database to search for and retrieve intended records (search as of October 5, 2024). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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