Relationship between the fibrinolytic profile and hemorrhagic in early pregnancy after in vitro fertilization

Objective - to evaluate the association between the fibrinolytic profile and the risk of hemorrhagic complications at 5-8 weeks of gestation following in vitro fertilization (IVF) in an ovulation induction cycle. Materials and methods. A retrospective post hoc study of 21 women with pregnancies achieved via IVF in an ovulation induction cycle was conducted. The fibrinolytic profile served as the independent variable, specifically: concentrations of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), and urokinase (uPA), along with the activities of plasminogen, α2-antiplasmin, and thrombin-activatable fibrinolysis inhibitor (TAFI). The dependent variable was the occurrence of hemorrhagic complications at 5-8 weeks of gestation, including subchorionic hematomas (SCH) and/or bleeding. To evaluate the association between variables, a multiple ridge logistic regression was employed, followed by validation and assessment of discriminative capacity via bootstrapping. Results. Subchorionic hematoma without bleeding was diagnosed in 3 women (14,3%), SCH with bleeding in 4 (19,1%), and bleeding without SCH in 3 (14,3%). Consequently, hemorrhagic complications were recorded in 10 women (47,6%). Regression analysis revealed that α2-antiplasmin and plasminogen were the only statistically significant predictors, with odds ratios (OR) of 1,63 (95% confidence interval (CI): 1,15; 2,1; p=0,008) and 1,27 (95% CI: 1,08; 1,41; p=0,012), respectively. The resulting model demonstrated acceptable discriminative capacity, with an area under the receiver operating characteristic curve (AUC-ROC) of 0,77 (95% CI: 0,61; 0,92). Conclusion. This study identified an association between the fibrinolytic profile - specifically α2-antiplasmin and plasminogen levels - and the risk of subchorionic hematoma and/or bleeding at 5-8 weeks of gestation in pregnancies achieved via IVF within an ovulation induction cycle.

1. Tocariu R., Stan D., Mitroi R.F., Căldăraru D.E., Dinulescu A., Dobre C.E., Brătilă E. Incidence of complications among in vitro fertilization pregnancies. J Med Life. 2023;16(3):399-405. DOI: 10.25122/jml-2023-0048. EDN: MEPPDR.

2. Bentov Y., Schenker J. IVF and pregnancy outcomes: the triumphs, challenges, and unanswered questions. J Ovarian Res. 2025;18:228. DOI: 10.1186/s13048-025-01692-5. EDN: EHQSBZ.

3. Zanettoullis A.T., Mastorakos G., Vakas P., Vlahos N., Valsamakis G. Effect of Stress on Each of the Stages of the IVF Procedure: A Systematic Review.Int J Mol Sci. 2024;25(2):726. DOI: 10.3390/ijms25020726. EDN: YRNZUM.

4. Lokshin V.N., Kutsenko I.I., Borovikov I.O., Bulgakova V.P., Kravtsova E.I., Biryukova M.I., Borovikova O.I., Nikogda J.V. Chronic endometritis and infertility - in vitro fertilization outcomes: systematic review and meta-analysis. Kuban Scientific Medical Bulletin. 2023;30(5):15-40 (in Russ.). DOI: 10.25207/1608-6228-2023-30-5-15-40. EDN: KXNPHH.

5. Yi X., Zhaxicuo, Tian D. Risk Factors of Subchorionic Hematoma Under Assisted Reproductive Technology. J Obstet Gynaecol Res. 2025;51(12):e70142. DOI: 10.1111/jog.70142. EDN: MTEUUS.

6. Xu T., Lun W., Wang P., He Y. Analysis of risk factors and pregnancy outcomes in pregnant women with subchorionic hematoma. Medicine (Baltimore). 2023;102(47):e35874. DOI: 10.1097/MD.0000000000035874. EDN: TJPTNY.

7. Hoirisch-Clapauch S. The Impact of Emotional Responses on Female Reproduction: Fibrinolysis in the Spotlight. Semin. Thromb. Hemost. 2025;51(4):401-411. DOI: 10.1055/s-0044-1788324. EDN: SNXLUP.

8. Wei W., Qiu X.C., Tang N., Liang Z., Wu J., Huang P. Incidence of subchorionic hematoma and contributing factors in assisted reproductive technologies - a retrospective cohort study. Front Med (Lausanne). 2025;12:1569789. DOI: 10.3389/fmed.2025.1569789. EDN: LDIIBN.

9. Sokolova N.V., Zanin S.A. Relationship of hemostasis indicators with development complications of pregnancy, that occurred in as a result of the use of auxiliary reproductive technologies. Crimean journal of experimental and clinical medicine. 2024;14(4):54-61. (in Russ.). DOI: 10.29039/2224-6444-2024-14-4-54-61. EDN: YFCOTK.

10. Sinkov S.V., Zabolotskikh I.B. Diagnosis and correction of hemostasis system disorders. 2rd ed. Moscow: Prakticheskaya meditsina, 2017. 336 p. (in Russ.)

11. Harrell F.E. Jr. rms: Regression Modeling Strategies. R package version 8.1-1. 2026. URL: https://CRAN.R-project.org/package=rms

12. Robin X., Turck N., Hainard A., Tiberti N., Lisacek F., Sanchez J.C., Müller M. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;12:77. DOI: 10.1186/1471-2105-12-77.

13. Khoddam A., Miyata T., Vaughan D. PAI-1 is a common driver of aging and diverse diseases. Biomed J. 2025;49(1):100892. DOI: 10.1016/j.bj.2025.100892. EDN: MRIKEE.

14. Miyata T. Overview: PAI-1 inhibitors and clinical applications. Biomed J. 2025;49(1):100874. DOI: 10.1016/j.bj.2025.100874. EDN: NZQFXS.

15. Wu J., Wang J., Pei Z., Zhu Y., Zhang X., Zhou Z., Ye C., Song M., Hu Y., Xue P., Zhao G. Endothelial senescence induced by PAI-1 promotes endometrial fibrosis. Cell Death Discov. 2025;11(1):89. DOI: 10.1038/s41420-025-02377-0. EDN: KJFFMV.