Features of the histological structure of the placenta in women with recurrent miscarriage depending on polymorphic variants of the metalloproteinase and hemostasis systems

The article is devoted to the analysis of the morphological characteristics of placental tissue in women with early reproductive losses with recurrent miscarriage, depending on the presence of polymorphic variants of metalloproteinases and hemostasis. It was established that in women with recurrent miscarriage, the area of the trophoblast of the placenta is significantly larger (р < 0.003), the area of the chorionic villi is smaller (р < 0.04) than in the group of women with implemented reproductive function. Thrombosis of the chorionic vessels, necrosis and calcinates in the placenta with PNF were detected in 80.0 % (р = 0.001), 93.3 % (р = 0.001), and 30.0 % (р = 0.049) of cases, respectively, which is significantly higher than in the comparison group. In patients with PNP with the T/T genotype of the 735 C/T polymorphism of the MMP-2 gene, the trophoblast area is significant (р < 0.05) more than with the C/C genotype, acute full-back (р = 0.02) and intervillous hemorrhage (р = 0.02). In women with the C/T genotype of the polymorphism 735 C/T of the MMP-2 gene, edema and dystrophic changes in the chorionic villi, placental necrosis are determined more often (р = 0.02) than with the C/C genotype. In carriers of the T allele of the polymorphism 735 C/T of the MMP-2 gene in the placenta, necrosis is significantly more common than in the CC genotype; the carriage of the T allele is also associated with large values of the relative area of the trophoblast and the stromal-intervillous relation, as well as with a smaller value of the ratio of the intervillous space area to the total area of the photograph.

1. Alonso A., Soto I., Urgellés M. F., Corte J. R., Rodríguez M. J., Pinto C. R. Acquired and inherited thrombophilia in women with unexplained fetal losses. American Journal of Obstetrics and Gynecology, 2002, vol. 187, no. 5, pp. 1337–1342. https://doi.org/10.1067/mob.2002.126849

2. Kutteh W. H., Triplett D. Thrombophilias and recurrent pregnancy loss. Seminars in Reproductive Medicine, 2006, vol. 24, no. 01, pp. 054–066. https://doi.org/10.1055/s-2006-931801

3. Krabbendam I., Franx A., Bots M. L., Fijnheer R., Bruinse H. W. Thrombophilias and recurrent pregnancy loss: a critical appraisal of the literature. European Journal of Obstetrics and Gynecology and Reproductive Biology, 2005, vol. 118, no. 2, pp. 143–153. https://doi.org/10.1016/j.ejogrb.2004.07.019

4. Peresada O. A. Modern approaches to the treatment of miscarriage. Meditsinskie novosti [Medical news], 2015, no. 5, pp. 28–30 (in Russian).

5. Kulakov V. I., Serov V. N., Barashnev Yu. I., Frolova O. G., Antonov A. G. Safe motherhood guide. Moscow, Triada-X Publ., 1998. 531 p. (in Russian).

6. Jordaan D.-J., Schoon M. G., Badenhorst P. N. Thrombophilia screening in pregnancy. Obstetrical and Gynecological Survey, 2005, vol. 60, nо. 6, pp. 394–404. https://doi.org/10.1097/01.ogx.0000165116.96026.4e

7. Public health in the Republic of Belarus: official statistical compilation for 2015. Minsk, Republican Scientific Medical Library Publ., 2016. 277 p. (in Russian).

8. Yakutovskaya S. L., Silyava V. L., Vavilova L. V. Pregnancy miscarriage (etiology, pathogenesis, diagnosis, clinic, treatment). Minsk, Belarusian Medical Academy of Postgraduate Education Publ., 2004. 44 p. (in Russian).

9. Agadzhanova A. A. Modern methods of treatment of patients with recurrent miscarriage. Russkii meditsinskii zhurnal = Russian Medical Journal, 2003, vol. 11, no. 1, pp. 3–6 (in Russian).

10. Farahmand K., Totonchi M., Hashemi M., Sabet F. R., Kalantari H., Gourabi H., Meybodi A. M. Thrombophilic genes alterations as risk factor for recurrent pregnancy loss. Journal of Maternal-Fetal and Neonatal Medicine, 2015, vol. 29, no. 8, pp. 1269–1273. https://doi.org/10.3109/14767058.2015.1044431

11. Rebrikov D. V., Trofimov D. Yu. Real-time PCR: a review of approaches to data analysis. Applied Biochemistry and Microbiology, 2006, vol. 42, no. 5, pp. 455–463. https://doi.org/10.1134/s0003683806050024

12. Radzinskii V. E. (ed.). Obstetrics. Moscow, GEOTAR-Media Publ., 2008. 898 p. (in Russian).

13. Many A., Schreiber L., Rosner S., Lessing J. B., Eldor A., Kupferminc M. J. Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia. Obstetrics and Gynecology, 2001, vol. 98, no. 6, рр. 1041– 1044. https://doi.org/10.1097/00006250-200112000-00010

14. Sidel’nikova V. M., Sukhikh G. T. Miscarriage of pregnancy. Мoscow, Medical News Agency Publ., 2010. 534 р. (in Russian).

15. Heit J. A. Thrombophilia: common questions on laboratory assessment and management hematology. Hematology, 2007, vol. 1, pp. 127–135. https://doi.org/10.1182/asheducation-2007.1.127

16. Sergi C., Al Jishi T., Walker M. Factor V Leiden mutation in women with early recurrent pregnancy loss: a meta-analysis and systematic review of the causal association. Archives of Gynecology and Obstetrics, 2015, vol. 291, no. 3, pp. 671–679. https://doi.org/10.1007/s00404-014-3443-x

17. Ren A., Wang J. Methylenetetrahydrofolate reductase C677T polymorphism and the risk of unexplained recurrent pregnancy loss: a meta-analysis. Fertility and Sterility, 2006, vol. 86, no. 6, pp. 1716–1722. https://doi.org/10.1016/j. fertnstert.2006.05.052

18. Bitsadze V. O., Makatsariya A. D., Khizroeva D. Kh., Makatsariya N. A., Yashenina E. V. Thrombophilia as the most important link in the pathogenesis of pregnancy complications. Prakticheskaya meditsina [Practical medicine], 2012, vol. 5, no. 60, pp. 22–29 (in Russian).

19. Armstrong E. M., Bellone J. M., Hornsby L. B., Treadway S., Phillippe H. M. Acquired thrombophilia. Journal of Pharmacy Practice, 2014, vol. 27, no. 3, pp. 234–242. https://doi.org/10.1177/0897190014530424

20. Benedetto C., Marozio L., Tavella A. M., Salton L., Grivon S., Giampaolo F. D. Coagulation disorders in pregnancy: acquired and inherited thrombophilias. Annals of the New York Academy of Sciences, 2010, vol. 1205, no. 1, pp. 106–117. https://doi.org/10.1111/j.1749-6632.2010.05674.x

21. Belfort M. A. Placenta accreta. Publications Committee, Society for Maternal-Fetal Medicine. American Journal of Obstetrics and Gynecology, 2010, vol. 203, no. 5, pp. 430–439. https://doi.org/10.1016/j.ajog.2010.09.013

22. Kravtsova G. I., Kletskii S. K. Clinical and morphological study of the placenta. Minsk, Minsk State Medical Institute Publ., 1995. 52 р. (in Russian).

23. Milovanov A. P. Pathology of the mother–placenta–fetus system: a guide for physicians. Moscow, Meditsina Publ., 1999. 446 р. (in Russian).

24. Korzhevskii D. E., Gilyarov A. V. The basics of histological technology. St. Petersburg, SpetsLit Publ., 2010. 95 р. (in Russian).