DOI: https://doi.org/10.14710/jbtr.v12i2.31422

The Importance of Prenatal Diagnosis in the Investigation of Recurrent Pregnancy Loss: A Transition from Screening to Diagnostics

Biomedical student, Department of Biomedical Sciences, Faculty of Medicine, YARSI University, Indonesia

Received: 25 Feb 2026; Revised: 22 Apr 2026; Accepted: 4 Jun 2026; Available online: 29 Aug 2026; Published: 31 Aug 2026.
Open Access Copyright (c) 2026 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

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Abstract

Recurrent pregnancy loss is a complex reproductive health problem that affects a significant proportion of women of reproductive age and is associated with substantial psychological, social, and economic burdens. Despite advances in reproductive medicine, the underlying cause remains unidentified in more than half of affected cases. This review aims to summarize current evidence regarding the etiological factors of recurrent pregnancy loss and to evaluate the role of prenatal diagnostic approaches in its investigation and management. The article discusses major contributing factors, including genetic, anatomical, endocrine, immunological, thrombophilic, and environmental influences. Furthermore, recent developments in non-invasive and invasive prenatal testing, chromosomal microarray analysis, whole-exome sequencing, parental karyotyping, and preimplantation genetic testing are reviewed. The importance of genetic counseling in supporting clinical decision-making and patient understanding is also highlighted. By integrating contemporary diagnostic technologies with multidisciplinary clinical care, prenatal diagnosis offers valuable insights into disease mechanisms and facilitates individualized management strategies. This review emphasizes the need for comprehensive evaluation and appropriate counseling to improve reproductive outcomes and reduce the emotional and financial burden experienced by affected couples.

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Keywords: Recurrent pregnancy loss; prenatal diagnosis; genetic testing; preimplantation genetic testing; genetic counseling

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Article Info
Section: Review Articles
Language : EN
  1. Himpunan Endokrinologi Reproduksi dan Fertilitas Indonesia (HIFERI), Perkumpulan Obstetri dan Ginekologi Indonesia (POGI). Konsensus Keguguran Berulang. Jakarta; 2018. Report
  2. Evaluation and treatment of recurrent pregnancy loss: A committee opinion. Fertil Steril. 2012 Nov;98(5):1103–11. doi: 10.1016/j.fertnstert.2012.06.048PubMedPMID:22835448
  3. Hennessy M, Dennehy R, Matvienko-Sikar K, O’Sullivan-Lago R, Uí Dhúbhgáin J, Lucey C, et al. Views of knowledge users on recurrent miscarriage services and supports in the Republic of Ireland: a qualitative interview study. BMJ Open. 2025 Apr 10;15(4). doi: 10.1136/bmjopen-2024-094753PubMedPMID:40216432
  4. Shalou ER, Polyakov A. Clinical care for women seeking pregnancy after miscarriage. Aust J Gen Pract. 2024;53(11):800–3. doi: 10.31128/AJGP-08-23-6931PubMedPMID:39499833
  5. Bosire A, Kosgei R, Gathara D, Madadi M, Osoti A. Burden, causes, and treatment approaches of recurrent pregnancy loss: a scoping review. Pan African Medical Journal . African Field Epidemiology Network; 2025. doi: 10.11604/pamj.2025.52.109.46376
  6. Committee on Genetics and the Society for Maternal-Fetal Medicine. Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology. ObstetGynecol. 2016 Dec;128(6):262–3. doi: 10.1097/AOG.0000000000001817.PubMedPMID:27875474
  7. Pauta M, Martinez-Portilla RJ, Jara-Ettinger AC, Ardiles-Ruesjas V, Borrell A. Genome-Wide Cell-Free DNA Analysis for Aneuploidy Detection in Miscarriages: Test Performance Meta-Analysis. Prenatal Diagnosis. John Wiley and Sons Ltd; 2025. doi: 10.1002/pd.6824
  8. Wan X, Li L, Liu Z, Fan Z, Yu L. Recurrent spontaneous abortion related to balanced translocation of chromosomes: two case reports. J Med Case Rep. 2021 Dec 1;15(1). doi: 10.1186/s13256-021-02848-9PubMedPMID:34024271
  9. Li Q, Chen S, Dong X, Fu S, Zhang T, Zheng W, et al. The Progress of Research on Genetic Factors of Recurrent Pregnancy Loss. Genetics Research. Hindawi Limited; 2023. doi: 10.1155/2023/9164374PubMedPMID:37006462
  10. Cao C, Bai S, Zhang J, Sun X, Meng A, Chen H. Understanding recurrent pregnancy loss: Recent advances on its etiology, clinical diagnosis, and management. Medical Review. Walter de Gruyter GmbH; 2022. p. 570–89. doi: 10.1515/mr-2022-0030
  11. Verdoni A, Hu J, Surti U, Babcock M, Sheehan E, Clemens M, et al. Reproductive outcomes in individuals with chromosomal reciprocal translocations. Genetics in Medicine. 2021 Sep 1;23(9):1753–60. doi: 10.1038/s41436-021-01195-wPubMedPMID:33972719
  12. Araszkiewicz AF, Jańczak K, Wójcik P, Białecki B, Kubiak S, Szczechowski M, et al. MTHFR Gene Polymorphisms: A Single Gene with Wide-Ranging Clinical Implications—A Review. Genes (Basel). 2025;16(4):1–27. doi: 10.3390/genes16040441PubMedPMID:40282401
  13. Turesheva A, Aimagambetova G, Ukybassova T, Marat A, Kanabekova P, Kaldygulova L, et al. Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box. Journal of Clinical Medicine. Multidisciplinary Digital Publishing Institute (MDPI); 2023. doi: 10.3390/jcm12124074
  14. Kirovakov Z, Gyokova EH, Hinkova NH, Konova EI. Recurrent pregnancy loss: etiology, pathophysiology, diagnosis and treatment. Journal of Biomedical and Clinical Research. 2025 Feb 5;18(1):1–10. doi: 10.3897/jbcr.e125766
  15. Yu T, Xu X, Wei Q. Non-Invasive Prenatal Testing: Advances, Applications, and Limitations in Prenatal Screening. Biomedical Research and Therapy . 2025;12(5):7418–23. doi: 10.15419/bmrat.v12i5.980
  16. Jayashankar SS, Nasaruddin ML, Hassan MF, Dasrilsyah RA, Shafiee MN, Ismail NAS, et al. Non-Invasive Prenatal Testing (NIPT): Reliability, Challenges, and Future Directions. Diagnostics. 2023;13(15):1–21. doi: 10.3390/diagnostics13152570PubMedPMID:37568933
  17. Poulton A, Hui L. Noninvasive prenatal testing: an overview. Aust Prescr. 2025 Apr 1;48(2):47–53. doi: 10.18773/austprescr.2025.019
  18. Flowers NJ, Med B, Sci L, Burgess T, Giouzeppos O, Shi G, et al. Genome-wide noninvasive prenatal screening for carriers of balanced reciprocal translocations. Genetics in Medicine. 2020;22:1944–55. doi: 10.1038/s41436
  19. Hu H, Wang L, Wu J, Zhou P, Fu J, Sun J, et al. Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 8141 single pregnancies. Hum Genomics. 2019;13. doi: 10.1186/S40246-019-0198-2PubMedPMID:30871627
  20. Liehr T. False-positives and false-negatives in non-invasive prenatal testing (NIPT): what can we learn from a meta-analyses on > 750,000 tests? Mol Cytogenet. 2022;15(1):1–10. doi: 10.1186/s13039-022-00612-2
  21. Van den Veyver IB, Chandler N, Wilkins-Haug LE, Wapner RJ, Chitty LS. International Society for Prenatal Diagnosis Updated Position Statement on the use of genome-wide sequencing for prenatal diagnosis. Prenat Diagn. 2022 May 1;42(6):796–803. doi: 10.1002/pd.6157PubMedPMID:35583085
  22. Atik RB, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, et al. ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum Reprod Open. 2023;2023(1). doi: 10.1093/hropen/hoad002
  23. Săbău ID, Bohîlțea LC, Varlas V. The evolution of prenatal Whole Exome Sequencing: from cytogenetics to precision medicine. Archive of Clinical Cases. 2025 May 20;12(2):80–9. doi: 10.22551/2025.47.1202.10318
  24. Hsiao CH, Chen JS, Shiao YM, Chen YJ, Chen CH, Chu WC, et al. Prenatal Diagnosis Using Chromosomal Microarray Analysis in High-Risk Pregnancies. J Clin Med. 2022 Jul 1;11(13). doi: 10.3390/jcm11133624
  25. Tomkiewicz J, Darmochwał-Kolarz D. The Diagnostics and Treatment of Recurrent Pregnancy Loss. Journal of Clinical Medicine. Multidisciplinary Digital Publishing Institute (MDPI); 2023. doi: 10.3390/jcm12144768
  26. Zhuang J, Fu W, Gu L, Ye X, Wang J, Chen C. Etiological diagnosis of miscarriage by combining use of chromosomal microarray analysis and whole-exome sequencing. Eur J Med Res. 2025 Jul 1;30(1):528. doi: 10.1186/s40001-025-02709-x
  27. Gudapati S, Chaudhari K, Shrivastava D, Yelne S. Advancements and Applications of Preimplantation Genetic Testing in In Vitro Fertilization: A Comprehensive Review. Cureus. 2024 Apr 1. doi: 10.7759/cureus.57357

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