Analysis of the clinical efficacy of pathogenetically justified secondary prevention of early reproductive losses in women with РАІ-1 gene polymorphism
DOI:
https://doi.org/10.15574/HW.2025.6(186).4455Keywords:
miscarriage, thrombophilia, pre-gravid preparation, haemostasis, oxidative stress, anticoagulants, lipids, immunological factors, prevention, complications, perinatal outcomesAbstract
Aim - to analyse the clinical efficacy of a pathogenetically justified method of secondary prevention of early reproductive losses in women with РAІ-1 gene polymorphism.
Materials and methods. The selected patients (n=115) were divided into three groups according to their genotype: Group I (n=20) - patients with the wild-type 675 5G>5G genotype of the PAI-1 gene; Group II (n=53) - women with the heterozygous 675 5G>4G polymorphism; Group III (n=42) - women with the homozygous 675 4G>4G polymorphism. Based on the study results and identified associative links, a method for secondary prevention of early reproductive losses was developed to reduce the manifestations and impact of endothelial dysfunction.
Results. The average age of women in the thematic groups was comparable and amounted to 32,5±0,9, 33,9±0,7 and 33,6±0,7 years, respectively. Correlation analysis revealed significant associations between hemostatic parameters, lipid metabolism, immunological factors, and pregnancy loss, depending on the PAI-1 gene polymorphism type. It was demonstrated that early pregnancy loss results from a complex interaction of genetic, metabolic, immune, and hemostatic factors.
Conclusions. Timely correction of endothelial dysfunction manifestations at the pre-pregnancy stage with a combination of sulodexide and ezetimibe appears to be a promising approach in terms of minimizing pregnancy complications due to their ability to restore the endothelium and promote normalization of PAI-1 production at the level of its genotype transcription.
The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
References
Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C et al. (2017). Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 27: 315-389. https://doi.org/10.1089/thy.2016.0457; PMid:28056690 PMCid:PMC5649398
Alijotas-Reig J, Garrido-Gimenez C. (2013). Current concepts and new trends in the diagnosis and management of recurrent miscarriage. Obstet Gynecol Surv. 68(6): 445-466. https://doi.org/10.1097/OGX.0b013e31828aca19; PMid:23942472
Arachchillage DRJ, Makris M. (2019). Inherited thrombophilia and pregnancy complications: should we test? Semin. Thromb. Hemost. 45: 50-60. https://doi.org/10.1055/s-0039-1692213; PMid:31195417
Bender AR, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S et al. (2018). ESHRE guideline: recurrent pregnancy loss. Hum. Reprod. Open. 2018: y4. https://doi.org/10.1093/hropen/hoy004; PMid:31486805 PMCid:PMC6276652
Bender AR, Christiansen OB, Elson J, Kolte AM, Sheena L, Middeldorp S et al. (2023). ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum. Reprod. Open. 2023(1): hoad002. https://doi.org/10.1093/hropen/hoad002; PMid:36873081 PMCid:PMC9982362
Cavalcante MB, Costa F da S, Araujo Junior E, Barini R. (2015). Risk factors associated with a new pregnancy loss and perinatal outcomes in cases of recurrent miscarriage treated with lymphocyte immunotherapy. J Matern Fetal Neonatal Med. 28: 1082-1086. https://doi.org/10.3109/14767058.2014.943175; PMid:25005857
Chester MR, Tirlapur A, Jayaprakasan K. (2022). Current management of recurrent pregnancy loss. The Obstetrician & Gynaecologist. 24: 260-271. https://doi.org/10.1111/tog.12832
Christiansen CH, Baum CM, Bass JD. (2011). The Person-Environment-Occupational Performance (PEOP) Model. In E. Duncan (Ed.), Foundations for practice in occupational therapy. 5th ed. Elsevier: 93-104.
Dobson SJA, Jayaprakasan KM. (2018). Aetiology of recurrent miscarriage and the role of adjuvant treatment in its management: a retrospective cohort review. J Obstet Gynaecol. 38: 967-974. https://doi.org/10.1080/01443615.2018.1424811; PMid:29557233
Dong AC, Morgan J, Kane M, Stagnaro-Green A, Stephenson MD. (2020). Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis. Fertil. Steril. 113(3): 587-600.e1. https://doi.org/10.1016/j.fertnstert.2019.11.003; PMid:32192591
Du Fosse NA, van der Hoorn MP, van Lith JMM, le Cessie S, Lashley E. (2020). Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis. Hum Reprod Update. 26: 650-669. https://doi.org/10.1093/humupd/dmaa010; PMid:32358607 PMCid:PMC7456349
Duka YuM. (2016). Patohenetychne obhruntuvannia diahnostyky, likuvalnoi taktyky ta profilaktyky vynyknennia systemnykh porushen u vahitnykh zhinok z nadmirnoiu masoiu tila. Dys. … d-ra med. nauk. Dnipro: 339.
Duka YuM. (2018). Materynska trombofiliia yak predyktor vynyknennia akusherskykh uskladnen ta perynatalnykh vtrat u zhinok iz nevynoshuvanniam vahitnosti zalezhno vid masy tila. Reproduktyvna endokrynolohyia. 42: 68-74. https://doi.org/10.18370/2309-4117.2018.42.68-74
Duka YuM, Panov VV. (2025). Kharakterystyka aktyvnosti pryrodnikh antykoahuliantiv u zhinok iz nevynoshuvanniam vahitnosti zalezhno vid vyiavlenoho polimorfizmu hena PAI-1 (675 5G/4G). Perspektyvy ta innovatsii nauky (Seriia "Psykholohiia", Seriia "Pedahohika", Seriia "Medytsyna"). (1): 2152-2165. https://doi.org/10.52058/2786-4952-2025-1(47)-2152-2165
Duncan EAS. (Ed.). (2006). Foundations for practice in occupational therapy. 4th ed. Philadelphia: Elsevier.
European Society of Human Reproduction and Embryology (ESHRE). (2017). Recurrent pregnancy loss. Strombeek-Bever: ESHRE; URL: https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Recurrent-pregnancy-loss.aspx.
Hennessy M, Dennehy R, Meaney S, Devane D, O'Donoghueet K. (2020). A protocol for a systematic review of clinical practice guidelines for recurrent miscarriage. HRB Open Res. 2; 3: 12. eCollection 2020. https://doi.org/10.12688/hrbopenres.13024.3; PMid:33005862 PMCid:PMC7477641
Hong LY, Marren A. (2018). Recurrent pregnancy loss: a summary of international evidence-based guidelines and practice. Aust. J. Gen. Pract. 47: 432-436. https://doi.org/10.31128/AJGP-01-18-4459; PMid:30114870
Jaslow CR, Carney JL, Kutteh WH. (2010, Mar 1). Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril. 93(4): 1234-1243. Epub 2009 Mar 31. https://doi.org/10.1016/j.fertnstert.2009.01.166; PMid:19338986
Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. (2006). Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum. Reprod Sep; 21(9): 2216-2222. https://doi.org/10.1093/humrep/del150; PMid:16707507
Iews M, Tan J, Taskin O, Alfaraj S, AbdelHafez FF et al. (2018). Does preimplantation genetic diagnosis improve reproductive outcome in couples with recurrent pregnancy loss owing to structural chromosomal rearrangement? A systematic review. Reprod Biomed Online. 36: 677-685. Epub 2018 Mar 15. https://doi.org/10.1016/j.rbmo.2018.03.005; PMid:29627226
Magnus MC, Wilcox AJ, Morken NH, Weinberg CR, Haberg SE. (2019). Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study. BMJ. 19; 364: l869. https://doi.org/10.1136/bmj.l869; PMid:30894356 PMCid:PMC6425455
Panov VV, Duka YuM. (2024). Comprehensive assessment of the hemostatic system in women with РAI-1 gene polymorphism and first trimester pregnancy loss. Ukrainian Journal Health of Woman. 6(175): 43-49. https://doi.org/10.15574/HW.2024.6(175).4349
Panov VV, Duka YuM. (2025). Analysis of the association of lipid profile parameters in women with first trimester pregnancy loss depending on PAI-1 gene polymorphism. Ukrainian Journal Health of Woman. 2(177): 4-10. https://doi.org/10.15574/HW.2025.2(177).410
Panov VV, Duka YuM. (2025). Comprehensive analysis of associative relationships between indicators of cellular-humoral immunity, pro- and anti-inflammatory cytokines in women with first trimester pregnancy loss depending on РАІ-1 gene polymorphism. Ukrainian Journal Health of Woman. 4(179): 28-38. https://doi.org/10.15574/HW.2025.4(179).2838
Panov VV, Duka YuM. (2025). Patohenetychno obgruntovani napriamky vtorynnoi profilaktyky rannikh reproduktyvnykh vtrat u zhinok iz nevynoshuvanniam vahitnosti ta nosiistvom polimorfizmu hena PAI-1 (675 5G/4G). Perspektyvy ta innovatsii nauky (Seriia "Psykholohiia", Seriia "Pedahohika", Seriia "Medytsyna"). 5(51): 3048-3066. https://doi.org/10.52058/2786-4952-2025-5(51)-3048-3066
Practice Committee of the American Society for Reproductive Medicine. (2012). Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 98: 1103-1111. https://doi.org/10.1016/j.fertnstert.2012.06.048; PMid:22835448
Practice Committee of the American Society for Reproductive Medicine. (2020). Evaluation and treatment of recurrent pregnancy loss. Fertil. Steril. 113: 533-535. https://doi.org/10.1016/j.fertnstert.2019.11.025; PMid:32115183
Rasmark RE, Christiansen OB, Kallen K, Hansson SR. (2021). Women with a history of recurrent pregnancy loss are a high-risk population for adverse obstetrical outcome: a retrospective cohort study. J. Clin. Med. 10: 179. https://doi.org/10.3390/jcm10020179; PMid:33419111 PMCid:PMC7825424
Rimmer MP, Fishwick K, Henderson I, Chinn D, Al Wattar BH, Quenby S. (2021). Quantifying CD138+ cells in the endometrium to assess chronic endometritis in women at risk of recurrent pregnancy loss: A prospective cohort study and rapid review. J. Obstet. Gynaecol. Res. 47(2): 689-697. https://doi.org/10.1111/jog.14585; PMid:33274569
Royal College of Obstetricians and Gynaecologists (RCOG). (2011). The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. Green-top guideline No. 17. London: RCOG. URL: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg17/.
Shargorodska E, Melenchuk L. (2022). Miscarriage: a modern perspective. Current issues in modern medicine: Bulletin of the Ukrainian Medical Dental Academy. 22(2)L 116-121. https://doi.org/10.31718/2077-1096.22.2.116
Smits RM, Mackenzie-Proctor R, Yazdani A, Stankiewicz MT, Jordan V, Showell MG. (2019, Mar 14). Antioxidants for male subfertility. Cochrane Database Syst. Rev. 3(3): CD007411. https://doi.org/10.1002/14651858.CD007411.pub4; PMid:30866036 PMCid:PMC6416049
Supramaniam PR, Mittal M, McVeigh E, Lim LN. (2018, Feb 27). The correlation between raised body mass index and assisted reproductive treatment outcomes: a systematic review and meta-analysis of the evidence. Reprod Health. 15(1): 34. https://doi.org/10.1186/s12978-018-0481-z; PMid:29486787 PMCid:PMC5830337
Ticconi C, Pietropolli A, Specchia M, Nicastri E, Chiaramonte C, Piccione E et al. (2020). Pregnancy-related complications in women with recurrent pregnancy loss: a prospective cohort study. J. Clin. Med. 9: 2833. https://doi.org/10.3390/jcm9092833; PMid:32882985 PMCid:PMC7564138
Van Dijk MM, Kolte AM, Limpens J, Kirk E, Quenby S, van Wely M et al. (2020). Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis. Hum. Reprod. Update. 26: 356-367. https://doi.org/10.1093/humupd/dmz048; PMid:32103270 PMCid:PMC7161667
Vissenberg R, van den Boogaard E, van Wely M, van der Post JA, Fliers E, Bisschop PH et al. (2012, Jul). Treatment of thyroid disorders before conception and in early pregnancy: a systematic review. Hum Reprod Update. 18(4): 360-373. https://doi.org/10.1093/humupd/dms007; PMid:22431565
Woolner AMF, Nagdeve P, Raja EA, Bhattacharya S, Bhattacharya S. (2020, Dec). Family history and risk of miscarriage: A systematic review and meta-analysis of observational studies. Acta Obstet. Gynecol. Scand. 99(12): 1584-1594. https://doi.org/10.1111/aogs.13940; PMid:32557529
Yushchenko MI, Duka YuM. (2023). Assessment of genetic susceptibility to the occurrence of placenta-associated complications in pregnant women with retrochorial hematomas in the trimester I of pregnancy. Ukrainian Journal of Perinatology and Pediatrics. 1(93): 12-18. https://doi.org/10.15574/PP.2023.93.12
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Ukrainian Journal Health of Woman
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal UKRAINIAN JOURNAL «HEALTH OF WOMAN» is compatible with the vast majority of funders' of open access and self-archiving policies. The journal provides immediate open access route being convinced that everyone – not only scientists - can benefit from research results, and publishes articles exclusively under open access distribution, with a Creative Commons Attribution-Noncommercial 4.0 international license (СС BY-NC).
Authors transfer the copyright to the Journal UKRAINIAN JOURNAL «HEALTH OF WOMAN» when the manuscript is accepted for publication. Authors declare that this manuscript has not been published nor is under simultaneous consideration for publication elsewhere. After publication, the articles become freely available on-line to the public.
Readers have the right to use, distribute, and reproduce articles in any medium, provided the articles and the journal are properly cited.
The use of published materials for commercial purposes is strongly prohibited.
