Ukrainian Journal Health of Woman. 2025. 2(177): 26-35. doi: 10.15574/HW.2025.2(177).2635
Kharun I. L.
Shupyk National Healthcare University of Ukraine, Kyiv

For citation: Kharun IL. (2025). Mechanisms of developing recurrent miscarriage: the role of posttraumatic stress disorder. Ukrainian Journal Health of Woman. 2(177): 26-35. doi: 10.15574/HW.2025.2(177).2635
Article received: Feb 08, 2025. Accepted for publication: Apr 22, 2025.

The rapid deterioration of the demographic situation in Ukraine highlights the particular significance of recurrent pregnancy loss (RPL). An insufficient assessment of the impact of post-traumatic stress disorder (PTSD) represents a significant gap in the current practices of diagnosis, treatment, and prevention of RPL.
Aim – to identify the relationship between PTSD and RPL, and to establish a probable correlation between the severity of PTSD and dysfunction in various systems of the female body.
Materials and methods. The study involved 150 women diagnosed with RPL. Depending on the presence of PTSD, participants were divided into four groups. Standardized psychodiagnostic tools (Posttraumatic Stress Disorder Checklist for Civilians (PCL-C), Clinician-Administered PTSD Scale (CAPS-5) a structured interview, Beck Depression Inventory) were used alongside clinical-laboratory, immunological, and hormonal assessment methods.
Results. A statistically significant association was found between PTSD and elevated levels of NK cells, indicating activation of innate immunity. Women with PTSD more frequently presented with thyroid dysfunction, antiphospholipid syndrome, and lifestyle-related risk behaviors, such as excessive caffeine intake, alcohol consumption, and smoking.
Conclusions. PTSD is an important risk factor for RPL and should be considered within interdisciplinary support programs for women with reproductive failures. The findings underscore the relevance of a comprehensive approach, including mandatory psycho-emotional assessment and intervention.
The study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the local ethics committee of the participating institution. Informed consent was obtained from all participants.
The author declares no conflict of interest.
Keywords: recurrent pregnancy loss, post-traumatic stress disorder, immune system, NK cells, thyroid dysfunction, antiphospholipid syndrome, psycho-emotional state, lifestyle factors, reproductive losses, psychosomatic disorders.
REFERENCES

1. Aoki K, Kajiura S, Matsumoto Y, Ogasawara MS, Okada S et al. (1995). Preconceptional natural-killer-cell activity as a predictor of miscarriage. The Lancet. 345: 1340-1342. https://doi.org/10.1016/S0140-6736(95)92539-2; PMid:7752757

2. Bezsheiko V. (2016, Sep). Adaptation of the Scale for Clinical Diagnosis of PTSD and the PTSD Symptom Checklist for the Ukrainian population. PMGP [online]. 19; 1(1): e010108. URL: https://uk.e-medjournal.com/index.php/psp/article/view/8.

3. Clifford K, Rai R, Watson H, Regan L. (1994, Jul 1). Pregnancy: An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases. Human Reproduction. 9; 7: 1328-1332. https://doi.org/10.1093/oxfordjournals.humrep.a138703; PMid:7962442

4. Cohen M, Meisser A, Bischof P. (2006, Aug). Metalloproteinases and human placental invasiveness. Placenta. 27(8): 783-793. Epub 2005 Oct 24. https://doi.org/10.1016/j.placenta.2005.08.006; PMid:16249026

5. Coomarasamy A, Dhillon-Smith RK, Papadopoulou A, Al-Memar M, Brewin J, Abrahams VM et al. (2021, May 1). Recurrent miscarriage: evidence to accelerate action. Lancet. 397(10285): 1675-1682. Epub 2021 Apr 27. https://doi.org/10.1016/S0140-6736(21)00681-4; PMid:33915096

6. 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. Fertility and sterility. 113(3): 587-600.e1. https://doi.org/10.1016/j.fertnstert.2019.11.003; PMid:32192591

7. Giouleka S, Tsakiridis I, Arsenaki E, Kalogiannidis I, Mamopoulos A, Papanikolaou E et al. (2023, May). Investigation and Management of Recurrent Pregnancy Loss: A Comprehensive Review of Guidelines. Obstet Gynecol Surv. 78(5): 287-301. https://doi.org/10.1097/OGX.0000000000001133; PMid:37263963

8. Horbatiuk OH. (2019). Features of women's reproductive dysfunctions associated with prolonged stressful situations. Zaporozhye medical journal. 21; 6(117): 764-769. URL: http://zmj.zsmu.edu.ua/article/view/186501/187014. https://doi.org/10.14739/2310-1210.2019.6.186501

9. Kaminskyi A, Kharun I. (2023, May). Obgruntuvannia vzaiemozv'iazku ta "efektu zamknenoho tsyklu" mizh posttravmatychnym stresovym rozladom ta zvychnym nevynoshuvanniam vahitnosti. Reproduktyvne zdorov'ia zhinky. 3: 18-23. https://doi.org/10.30841/2708-8731.3.2023.283319

10. Kwak JY, Beaman KD, Gilman-Sachs A, Ruiz JE, Schewitz D, Beer AE. (1995). Up-regulated expression of CD56+, CD56+/CD16+, and CD19+ cells in peripheral blood lymphocytes in pregnant women with recurrent pregnancy losses. American journal of reproductive immunology (New York, N.Y.: 1989). 34(2): 93-99. https://doi.org/10.1111/j.1600-0897.1995.tb00924.x; PMid:8526995

11. Lazarides C, Moog NK, Verner G, Voelkle MC, Henrich W, Heim CM et al. (2023). The Association between History of Prenatal Loss and Maternal Psychological State in a Subsequent Pregnancy: an Ecological Momentary Assessment (EMA) Study. Psychological Medicine. 53(3): 855-865. https://doi.org/10.1017/S0033291721002221; PMid:34127159 PMCid:PMC9975992

12. Mosaddegh MH, Ghasemi N, Jahaninejad T, Mohsenifar F, Aflatoonian A. (2012). Treatment of recurrent pregnancy loss by Levothyroxine in women with high Anti-TPO antibody. Iranian journal of reproductive medicine. 10(4): 373-376.

13. MOZ Ukrainy. (2008). Pro vnesennia zmin do nakazu MOZ Ukrainy vid 15 hrudnia 2003 roku. Klinichnyi protokol «Nevynoshuvannia vahitnosti». Nakaz MOZ Ukrainy vid 03.11.2008 r. No 624. URL: https://zakon.rada.gov.ua/rada/show/v0624282-08#Text.

14. MOZ Ukrainy. (2016). Unifikovanyi klinichnyi protokol pervynnoi, vtorynnoi (spetsializovanoi) ta tretynnoi (vysokospetsializovanoi) medychnoi dopomohy. «Reaktsiia na vazhkyi stres ta rozlady adaptatsii. Posttravmatychnyi stresovyi rozlad». Nakaz MOZ Ukrainy vid 23.02.2016 No 121. URL: https://dec.gov.ua/wpcontent/uploads/images/dodatki/2016_121_PTSR/2016_121_YKPMD_PTSRpdf?fbclid=IwAR067yDcA17RTxg67qO3m5jk6gnQmaS5HAe49cy0WzBggEciVhmhD_hTg7k.

15. Natsionalnyi Tsentr PTSD. (1993). PCL – shkala samootsinky naiavnosti PTSR. Boston, USA. URL: https://i-cbt.org.ua/wp-content/uploads/2017/11/PCL_ПТСР.pdf.

16. Ng KYB, Cherian G, Kermack AJ, Bailey S, Macklon N et al. (2021). Systematic review and meta-analysis of female lifestyle factors and risk of recurrent pregnancy loss. Scientific reports. 11(1): 7081. https://doi.org/10.1038/s41598-021-86445-2; PMid:33782474 PMCid:PMC8007745

17. Papas R, Kutteh W. (2020). A new algorithm for the evaluation of recurrent pregnancy loss redefining unexplained miscarriage: review of current guidelines. Current Opinion In Obstetrics & Gynecology. 32(5): 371-379. https://doi.org/10.1097/GCO.0000000000000647; PMid:32590384

18. Pluchino N, Drakopoulos P, Wenger JM, Petignat P, Streuli I, Genazzani AR. (2014). Hormonal causes of recurrent pregnancy loss (RPL). Hormones (Athens, Greece). 13(3): 314-322. https://doi.org/10.14310/horm.2002.1505; PMid:25079455

19. Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M, Stephenson MD, Fisher J et al. (2021). Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet (London, England). 397(10285): 1658-1667. https://doi.org/10.1016/S0140-6736(21)00682-6; PMid:33915094

20. Regan L, Rai R, Saravelos S, Li TC; Royal College of Obstetricians and Gynaecologists. (2023, Nov). Recurrent MiscarriageGreen-top Guideline No. 17. BJOG. 130(12): e9-e39. Epub 2023 Jun 19. https://doi.org/10.1111/1471-0528.17515; PMid:37334488

21. Rozov VI. (2024). Beck Hopelessness Scale // Psychology of extreme situations: adaptability to stress and psychological support: a scientific and practical guide. Kyiv: KNT: 687.

22. Schalin-Jäntti C. (2017). Autoimmune thyroiditis. Guidelines 00512. EBM Guidelines Internal medicine Endocrinology. URL: https://guidelines.moz.gov.ua/documents/3348.

23. Schneid-Kofman N, Sheiner E, Levy A. (2008, Apr). Psychiatric illness and adverse pregnancy outcome. Int J Gynaecol Obstet. 101(1): 53-56. Epub 2007 Dec 20. https://doi.org/10.1016/j.ijgo.2007.10.007; PMid:18082746

24. Stefanidou EM, Caramellino L, Patriarca A, Menato G. (2011). Maternal caffeine consumption and sine causa recurrent miscarriage. European journal of obstetrics, gynecology, and reproductive biology. 158(2): 220-224. https://doi.org/10.1016/j.ejogrb.2011.04.024; PMid:21636205

25. Tavoli Z, Mohammadi M, Tavoli A, Moini A, Effatpanah M et al. (2018, Jul 28). Quality of life and psychological distress in women with recurrent miscarriage: a comparative study. Health Qual Life Outcomes. 16(1): 150. https://doi.org/10.1186/s12955-018-0982-z; PMid:30055644 PMCid:PMC6064101

26. The ESHRE Guideline Group on RPL, Atik RB, Christiansen OB, Elson J, Kolte AM, Lewis Sh et al. (2023). ESHRE guideline: recurrent pregnancy loss: an update in 2022. Human Reproduction Open. 2023; 1: hoad002. https://doi.org/10.1093/hropen/hoad002; PMid:36873081 PMCid:PMC9982362

27. Van Wely M. (2023, Nov). Series of overviews on miscarriage and recurrent miscarriage. Fertil Steril.;120(5):932-933. Epub 2023 Sep 16. https://doi.org/10.1016/j.fertnstert.2023.09.006; PMid:37722471

28. Weathers FW, Blake DD, Schnurr PP, Kaloupek DG, Marx BP, Keane TM. (2013). .The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Interview available from the National Center for PTSD at http://www.ptsd.va.gov.

29. WHO. (1977). Recommended definitions, terminology and format for statistical tables related to the perinatal period and use of a new certificate for cause of perinatal deaths. Modifications recommended by FIGO as amended October 14, 1976. Acta Obstet Gynecol Scand. 56(3): 247-253. https://doi.org/10.3109/00016347709162009; PMid:560099