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Maternal Thrombophilic and Hypofibrinolytic Genetic Variants in Idiopathic Recurrent Pregnancy Loss: a Continuing Mystery

  • Reproductive Genetics: Original Article
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Abstract

Despite the fact that multiple recurrent pregnancy loss (RPL) etiologies have been identified, 50–70% of RPL cases remain enigmatic, and idiopathic RPL is still a serious medical challenge. A plethora of studies have investigated the correlation of RPL with variations in coagulation and/or fibrinolytic factors-encoding genes. Notwithstanding, evidence for a link between these variations and RPL remains discordant. We aimed to explore the association of thrombophilic and hypofibrinolytic gene variations with RPL development. Two hundred Saudi women were recruited in this study, comprising 150 women experiencing RPL and 50 healthy women. Thirteen genetic variants, including FV G1691A, FV A4070G, F2 G20210A, F13A1 G103T, FGB − 455G > A, PAI-1 − 675 4G/5G, ITGB3 T1565C, MTHFR C677T, MTHFR A1298C, ACE I/D, APOB G10708A, APOE T388C, and APOE C526T were genotyped using ViennaLab StripAssay. Women experiencing RPL harbor significantly higher frequencies of the F13A1 103 T, FGB − 455A, and ITGB3 1565C alleles than control women (p < 0.001). No differences in the prevalence of other investigated variants were identified between control women and those with RPL. No considerable link of F5 1691G > A/4070A > G, MTHFR 677C > T/1298A > C, and APOE 388 T > C/526C > T haplotypes with RPL risk was demonstrated. F13A1 G103T, FGB − 455G > A, and ITGB3 T1565C variants are connected to a higher likelihood of developing RPL and, hence, may have the potential to identify those women at risk of RPL, thereby, improving RPL susceptibility prediction. Incorporating molecular testing of thrombophilic and hypofibrinolytic genetic variants into routine workup could confer a promising approach for refined RPL risk assessment.

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Data Availability Statement

All data generated or analyzed during this study are included in this published article.

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Authors and Affiliations

  1. Department of Molecular Genetics, Al Borg Diagnostics, Jeddah, Kingdom of Saudi Arabia

    Mahmoud Younis

  2. Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, 11432, Kingdom of Saudi Arabia

    Mohamed A. M. Ali

  3. Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt

    Mohamed A. M. Ali & Shadia A. Fathy

  4. Bio-Screening and Preclinical Trial Lab, Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt

    Doaa A. Ghareeb

  5. Fetomaternal Ultrasound Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

    Rehab Youssef

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  1. Mahmoud Younis
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Contributions

Study conception and design: SAF, DAG, and MAMA; participant recruitment and clinical monitoring: RY; conducting of the molecular genetic investigations: MY; data acquisition: MY and MAMA; analysis and interpretation of data: MAMA and MY; conceptualization and drafting of the manuscript: MAMA and MY; critical revision of the manuscript: SAF, DAG, MAMA, and MY; all authors have approved the final manuscript.

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Correspondence to Mohamed A. M. Ali.

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All study protocols were in accordance with the 1964 Helsinki Declaration and its later amendments and approved by the local ethical committee.

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Younis, M., Ali, M.A.M., Ghareeb, D.A. et al. Maternal Thrombophilic and Hypofibrinolytic Genetic Variants in Idiopathic Recurrent Pregnancy Loss: a Continuing Mystery. Reprod. Sci. 30, 656–666 (2023). https://doi.org/10.1007/s43032-022-01063-1

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