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
. 2024 Jan-Dec:20:17455057241296608.
doi: 10.1177/17455057241296608.

Exploring the sophistications of unexplained recurrent pregnancy loss: A case-control study

Trinh Thi Que  1 , Nguyen Van The  2 , Vu Thi Thu Trang  3 , Le Van Truong  2 , Ta Thanh Van  4 , Doan Thi Kim Phuong  4   5
Affiliations

Exploring the sophistications of unexplained recurrent pregnancy loss: A case-control study

Trinh Thi Que et al. Womens Health (Lond). 2024 Jan-Dec.

Abstract

Background: Unexplained recurrent pregnancy loss (URPL) is a significant obstetric challenge affecting maternal health and well-being. Genetic factors, including mutations in the methylenetetrahydrofolate reductase (MTHFR) gene and elevated homocysteine levels, are increasingly recognized as contributors to URPL, though their precise roles remain complex. This study aimed to comprehensively explore these factors.

Objectives: This study examines the links between MTHFR gene polymorphisms (C677T and A1298C), plasma homocysteine levels, and URPL. It also aims to create a predictive model for URPL based on these factors.

Design: A case-control study with Vietnamese women who had at least one pregnancy between January 2017 and June 2020, recruited from Medlatec Hospital and Hanoi Medical University. Participants included URPL cases (n = 128) and controls (n = 126).

Methods: Participants were selected based on specific criteria. Main analyses identified the optimal multivariable logistic regression model for predicting URPL using Bayesian Model Averaging, with the optimal model chosen based on the highest Area Under the Curve (AUC) and posterior probability. A nomogram for clinical risk prediction was developed based on parameters from the optimal model.

Results: URPL cases exhibited significantly higher plasma homocysteine levels (11.73 ± 6.08 µmol/L) compared to controls (7.64 ± 1.78 µmol/L), correlating with increased URPL risk (OR: 1.64, 95% confidence interval (CI): 1.41-1.96; p < 0.001). The MTHFR C677T variant showed strong associations with URPL, particularly the CT genotype (OR: 6.07, 95% CI: 3.00-12.93; p < 0.001) and TT genotype (OR: 14.62, 95% CI: 2.85-114.77; p = 0.003). Similarly, the A1298C variant demonstrated elevated URPL risk with the AC genotype (OR: 2.73, 95% CI: 1.34-5.78; p = 0.007) and CC genotype (OR: 12.43, 95% CI: 3.17-64.22; p = 0.001).

Conclusion: This study provides insights into the complex interplay of MTHFR gene mutations, elevated homocysteine levels, and URPL. Genetic testing and biomarker assessment may play a crucial role in customizing risk assessment and management strategies for women at risk of URPL.

Keywords: A1298C; C677T; MTHFR; homocysteine; miscarriage.

PubMed Disclaimer

Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Nomogram chart predicts the risk of URPL for women. URPL, unexplained recurrent pregnancy loss.
See this image and copyright information in PMC

References

    1. Quenby S, Gallos ID, Dhillon-Smith RK, et al.. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet 2021; 397(10285): 1658–1667. - PubMed
    1. Page JM, Silver RM. Stillbirth: evaluation and follow-up. Obstet Gynecol Clin North Am 2020; 47(3): 439–451. - PubMed
    1. Heazell AEP, Siassakos D, Blencowe H, et al.. Stillbirths: economic and psychosocial consequences. Lancet Lond Engl 2016; 387(10018): 604–616. - PubMed
    1. Dimitriadis E, Menkhorst E, Saito S, et al.. Recurrent pregnancy loss. Nat Rev Dis Primer 2020; 6(1): 98. - PubMed
    1. Li YH, Marren A. Recurrent pregnancy loss: a summary of international evidence-based guidelines and practice. Aust J Gen Pract 2018; 47(7): 432–436. - PubMed

Substances

LinkOut - more resources