Correction of endothelial dysfunction as a part of preconception preparation of patients with metabolic syndrome and polycystic ovary syndrome: multidisciplinary approach: 618.11-008.64

Abstract

Summary. Background. Metabolic syndrome (MS) is a polyetiological condition, contributes to the potentiation of risks associated with thromboembolic and gestational complications. Sulodexide is a promising drug in the correction of endothelial dysfunction and contributes to both the prevention and treatment of thrombotic processes. Patients planning pregnancy require rational risks prophylaxis of metabolic and gestational complications, as well as unfavorable reproductive outcomes; however, in clinical proto- cols of Interdisciplinary Association of Reproductive Medicine Specialists (MARS) on preconception care there is no data of such an approach, that requires a comparative analysis and modification of existing algorithms. Objective: to optimize the principles of preconception care in patients with MS in order to improve reproductive outcomes and reduce the risk of vascular complications. Patients/Methods. A randomized controlled prospective study was performed, which included 80 patients aged 18 to 40 years with a verified diagnosis of MS and polycystic ovary syndrome (PCOS), as well as signs of chronic venous insufficiency (CVI), plan- ning pregnancy within 1 year. The patients were divided into 2 groups (control and comparison) of 40 women in each by simple randomization. All women received prescribed therapy according the clinical protocol for preconception care. In the scheme of preconception care for the comparison group sulodexide (endotheliotropic drug) was additionally included to prevent gestational complications and improve reproductive outcomes. Detailed study of hemostasis parameters (determination of platelet number, level of fibrinogen, antithrombin III, proteins C and S, homocysteine, values of prothrombin and thrombin time) and assessment of CVI severity before and after treatment was performed in all patients. Results. Preconception care, including sulodexide, contri- buted to a pronounced reduction of cytotoxic effect on the endothelium: homocysteine level decreased from 11.39 ± 0.59 μmol/l to 8.34 ± 0.62 μmol/l (p < 0.05) in the comparison group and from 10.62 ± 0.42 μmol/l to 9.57 ± 0.33 μmol/l (p > 0.05) in the control group. The frequency of pregnancy in the group using sulodexide — 18 (45.0%) patients was significantly (p < 0.05) higher compared with 13 (32.5%) patients in control group. The severity of CVI symptoms decreased in both groups after treatment, a more pronounced effect was observed in the group of patients using sulodexide; however, the question of statistical significance remains open due to the small number of patients that requires further studies. Conclusions. The combined effect with the use of endotheliotropic drugs as a part of preconception care for patients with MS contributes to a statistically significant increase in fertility, reduces the risk of thrombotic episodes and promotes correction of CVI symptoms.

References

1. Hunt B.J. Hemostasis at extremes of body weight. Semin Thromb Hemost. 2018;44(7):632–9. DOI: 10.1055/s0038–1661385.
2. Grandl G., Wolfrum C. Hemostasis, endothelial stress, inflammation, and the metabolic syndrome. Semin Immunopathol. 2018;40(2):215–24. DOI: 10.1007/s00281–017–0666–5.
3. Eating Disorders: recognition and treatment. Methods, evidence and recommendations. Clinical Guideline. London: National Institute for Health and Care Excellence, 2017. 970 p. Available at: https://www.nice.org.uk/guidance/ng69/evidence/fullguide linepdf161214767896.
4. Mousa A., Joham A., Boyle J. Polycystic ovary syndrome. Semin Reprod Med. 2021;39(3–04):69–70. DOI: 10.1055/s0041–1735506.
5. Teede H., Deeks A., Moran L. Polycystic ovary syndrome: a com plex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med. 2010;8:41. DOI: 10.1186/1741–7015–8–41.
6. Rees D.A., JenkinsJones S., Morgan C.L. Contemporary reproductive outcomes for patients with polycystic ovary syndrome: A retrospective observational study. J Clin Endocrinol Metab. 2016;101(4):1664–72. DOI: 10.1210/jc.2015–2682.
7. Lapina I.A., Chirvon T.G., Dobrokhotova Yu.E., Taranov V.V. Pre pregnancy preparation in women with polycystic ovary syndrome and obesity: stateoftheart. RMZh. Mat’ i ditya. 2021;4(2):137–43. (In Russ.). DOI: 10.32364/2618–8430–2021–4–2–137–143.
8. Gariani K., HugonRodin J., Philippe J. et al. Association between polycystic ovary syndrome and venous thromboembolism: A sys tematic review and metaanalysis. Thromb Res. 2020;185:102–8. DOI: 10.1016/j.thromres.2019.11.019.
9. Clinical guidelines. Varicose veins of the lower extremities. Moscow: Ministerstvo zdravoohraneniya Rossijskoj Federacii, 2021. 119 pp. (In Russ.). Available at: http://disuria.ru/_ld/10/1074_kr21I83MZ. pdf.
10. Carroll B.J., Piazza G., Goldhaber S.Z. Sulodexide in venous disease. J Thromb Haemost. 2019;17(1):31–8. DOI: 10.1111/jth.14324.
11. Jiang Q.J., Bai J., Jin J. et al. Sulodexide for secondary prevention of recurrent venous thromboembolism: A systematic review and metaanalysis. Front Pharmacol. 2018;9:876. DOI: 10.3389/fphar.2018.00876.
12. Pompilio G., Integlia D., Raffetto J., Palareti G. Comparative efficacy and safety of sulodexide and other extended anticoagulation treatments for prevention of recurrent venous thromboembolism: A Bayesian Network metaanalysis. TH Open. 2020;4(2): e80e93. DOI: 10.1055/s0040–1709731.
13. Bignamini A.A., Matuska J. Sulodexide for the symptoms and signs of chronic venous disease: a systematic review and metaanalysis. Adv Ther. 2020;37(3):1013–33. DOI: 10.1007/s12325–020–01232–1.
14. Pompilio G., Nicolaides A., Kakkos S.K., Integlia D. Systematic literature review and network Metaanalysis of sulodexide and other drugs in chronic venous disease. Phlebology. 2021;36(9):695– 709. DOI: 10.1177/02683555211015020.
15. Masola V., Zaza G., Onisto M. et al. Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: biological roles and pharmacological effects. Int Angiol. 2014;33(3):243–54.
16. Raffetto J.D., Yu W., Wang X. et al. Sulodexide improves contraction and decreases matrix metalloproteinase2 and –9 in veins under prolonged stretch. J Cardiovasc Pharmacol. 2020;75(3):211– 21. DOI: 10.1097/FJC.0000000000000778.
17. Clinical guidelines. Polycystic ovary syndrome. Moscow: Ministerstvo zdravoohraneniya Rossijskoj Federacii, 2021. 61 pp. (In Russ.). Available at: https://minzdrav.samregion.ru/wpcontent/uploads/ sites/28/2021/07/kr258.pdf.
18. Preconception preparation. Clinical protocol of the Interdisciplinary Association of Reproductive Medicine Specialists (MARS). Version 2.0. Moscow: Redakciya zhurnala Status Praesens, 2020. 128 pp. (In Russ.). Available at: https://spnavigator.ru/ document/0f9121c0–8f23–4c63a90adb955b90827a.