PROGESTER ONERECEPTION IN THE PERIPHERAL BLOOD MONONUCLEAR CELLS AND THE SUCCESS OF ASSISTED REPRODUCTIVE TECHNOLOGY

DOI: https://doi.org/10.29296/24999490-2018-01-11

E.N. Kareva (1, 2), D.A. Tikhonov (2), V.D. Kuvayeva (1), R.A. Velichinskii (1), M.P. Klimenko (3) 1-N.I. Pirogov Russian National Research Medical University, Ostrovitianova str., 1, Moscow, 117997, Russian Federation; 2-I.M.Sechenov First Moscow State Medical University, Trubetskaya str., 8–2, Moscow, 119991, Russian Federation 3-Clinical Municipal Hospital №31, Lobachevsky str., 42, Moscow, 119415, Russian Federation E-mail: [email protected]

Introduction. Low rate of the pregnancy frequency in the IVF programs is one of the challenges in gynaecology nowadays. One of the approaches to enhance the efficacy of the assisted reproductive technology is to estimate the success of the forthcoming procedure by evaluating parameters crucial for the implantation in each individual patient. Important factors to be considered for the success of the implantation include overall immune system status and progesterone receptor levels and their functional activity in immunocompetent cells. The aim of the study. Assessing levels of the gene expression of progesterone and oestrogen receptors and PIBF in the blood mononuclear cells of women participating in the IVF program. Methods. Density gradient centrifugation, peripheral blood mononuclear cells, RT-PCR. Results. We have shown the effective IVF cycle to be associated with significantly higher expression level of progesterone receptors PR-A, PR-B and PGRmC1 in cells of the peripheral blood mononuclear fraction (average 25-, 28-and 2.1-fold difference, respectively, р≤0,01) if compared to patients with unsuccessful attempts. Similar results were observed when analyzing the gene expression level of progesterone-induced blocking factor (PIBF) (2-fold difference, р=0,013). This parameter can be a novel predictive marker to estimate the efficacy of the IVF program. Conclusion. The results of the our study allow to predict the success of the treatment in the standard long IVF protocol. Data obtained in the study offer an opportunity to provide recommendations for the treatment tactics in IVF program patients, as well as allows suspend the procedure in case of the negative results and to procure hormonal treatment for the woman before the next attempt.
Keywords: 
IVF, peripheral blood mononuclear cells, efficacy prognosis

Список литературы: 
  1. Ata B., Yakin K., Balaban B., Urman B. Embryo implantation rates in natural and stimulated assisted reproduction treatment cycles in poor responders.ReprodBiomedOnline. 2008; 17 (2): 207–12.
  2. Tokmakov A.A., Fukami Ya. Vnegenomnye mehanizmy deystviya progesterona. Citologiya. 2009; 403–16.
  3. [Tokmakov A.A., Fukami J. Nongenomic mechanisms of action of progesterone. Cytology, 2009; 403–16 (in Russian)]
  4. Kareva E.N., Shimanovskiy N.L. Molekulyarnye mehanizmy deystviya gestagenov. Zh. e`ksp. i klinicheskaya farmakologiya. 2011; 74 (4): 36–42.
  5. [Kareva E.N., Shimanovsky N.L. Molecular mechanisms of action of progestogens. J. Exp. and clinical pharmacology. 2011; 74 (4): 36–42 (in Russian)]
  6. Cahill M.A. Progesterone receptor membrane component 1: an integrative review. J. Steroid Biochem. Mol. Biol. 2007; 105 (1–5): 16–36.
  7. Böyum A. Separation of leukocytes from blood and bone marrow. Introduction. Scand J. Clin. Lab Invest Suppl. 1968; 97 (21): 1–9.
  8. Savel`eva G.M., Shimanovskiy N.L., Klimenko P.A., Kareva E.N., Kappusheva L.M., Suknovalova M.V., Kramarenko M.P. Patent na izobretenie RF № 2430379 «Sposob prognozirovaniya nastupleniya beremennosti v programme e`kstrakorporal`nogo oplodotvoreniya i perenosa e`mbrionov v standartnom dlinnom protokole stimulyacii superovulyacii». 27 Sentyabrya 2011.
  9. [Savelyeva G.M., Szymanowski N.L., Klimenko P.A., Kareva E.N., Kappusheva L.M., Suknovalova M.V. Kramarenko M.P. Patent № 2430379 «Method for predicting pregnancy in vitro fertilization and embryo transfer in a standard long protocol of superovulation stimulation». September 27, 2011 (in Russian)]
  10. Radhupathy R. Functions of embryonic interferons and of the main serum proteins specific for pregnancy. Hum Reprod. 2000; 15: 713–8.
  11. Kareva E.N., Gankovskaya L.V., Shimanovskiy N.L. Polovye steroidy i immunitet. Rossiyskiy immunologicheskiy zhurnal. 2012; 6 (1–15): 3–13.
  12. [Kareva E.N., Gankovskaya L.V., Shimanovsky N.L. Sexsteroids and immunity. Russian J. of Immunology. 2012; 6 (1–15): 3–13 (in Russian)]
  13. Nakayama T(1), Fujiwara H., Maeda M., Inoue T., Yoshioka S., Mori T., Fujii S. Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances te effects of PBMC. Hum Reprod. 2002; 17 (1): 207–12.
  14. Szekeres-Bartho J., Polgar B. PIBF: The Double Edged Sword. Pregnancy and Tumor. Am. J. Reprod Immunol. 2010; 64: 77–86.
  15. Patel B., Elguero S., Thakore S., Dahoud W., Bedaiwy M., Mesiano S. Role of nuclear progesterone receptor isoforms in uterine pathophysiology. Hum Reprod Update. 2015; 21 (2): 155–73.
  16. Mesiano S., Wang Y., Norwitz E.R. Progesterone receptors in the human pregnancy uterus: do they hold the key to birth timing? Reprod Sci. 2011; 18 (1): 6–19.
  17. Conneely O.M. Progesterone receptors and ovulation. Handb Exp Pharmacol. 2010; 198: 37–44.