The role of the soluble fms-like tyrosin kinase-1 / the placental growth factor ratio in the diagnostics of preeclampsia in physiological pregnancy and pregnancy after IVF
Objective. To compare PlGF, sFlt-1 concentrations reference ranges and sFlt-1/PlGF ratio in normal pregnancies and pregnancies after IVF and to reveal special features of these markers synthesis in pregnancies complicated by preeclampsia depending on the severity of the disease.Ivanets T.Yu., Kan N.E., Tyutyunnik V.L., Bezzubenko Yu.V., Ibragimov R.R.
Subject and methods. 547 pregnant women were enrolled in the study. Control group included 347 pregnant women with normal pregnancies. Study group included 148 women with pregnancies complicated by preeclampsia, 56 pregnant women had mild preeclampsia, 92 pregnant women had severe preeclampsia. We studied 25 patients with uncomplicated pregnancies after IVF for preeclampsia markers comparative analysis in normal pregnancies and pregnancies after IVF.
Results. We obtained reference values of placental growth factor and soluble fms-like tyrosine kinase-1 and their ratio during normal pregnancy from 11-40 week of pregnancy. 90% of the values were within reference intervals for spontaneous uncomplicated pregnancy. The level of placental growth factor was lower the median value in 85% of all cases of pregnancies after IVF regardless of gestational age. Whereas the level of soluble fms-like tyrosine kinase-1 and sFlt-1/PlGF ratio were comparable to the levels of these markers in normal pregnancies. We revealed that sFlt-1/PlGF ratio is a significant marker of preeclampsia severity.
Conclusion. This study showed feasibility of the use of investigated markers both in spontaneous pregnancies and pregnancies after IVF without restriction. Moreover, we revealed sFlt-1/PlGF ratio diagnostic value in preeclampsia severity assessment. The obtained results are of clinical importance, since they allow us to recommend the wide use of these markers in clinical practice for preeclampsia diagnosis and prediction to reduce obstetric complications rate and to improve perinatal outcomes.
Keywords
preeclampsia
placental growth factor
soluble fms-like tyrosine kinase-1
IVF
Supplementary Materials
- Table 1. Clinical characteristics of pregnant women
- Тable 2. The levels of blood serum angiogenic markers and their ratio in pregnancy complicated by mild and severe preeclampsia depending on gestational age
- Fig.1. Placental growth factor concentration (pg/ml) in normal pregnancy after IVF and ET (median and 95% reference intervals (2,5 and 97,5 percentile) for spontaneous uncomplicated pregnancy are introduced for comparison)
- Fig.2. Soluble fms-like tyrosine kinase-1 concentration (pg/ml) in normal pregnancy after IVF and ET (median and reference intervals (2,5 and 97,5 percentile) for spontaneous uncomplicated pregnancy are introduced for comparison)
- Fig.3. sFlt-1/PlGF ratio in normal pregnancy after IVF and ET (median and reference intervals (2,5 and 97,5 percentile) for spontaneous uncomplicated pregnancy are introduced for comparison)
References
1. Серов В.Н., Кан Н.Е., Тютюнник В.Л. Прогностическое значение отношения растворимой fms-подобной тирозинкиназы-1 к плацентарному фактору роста у беременных с преэклампсией. Акушерство и гинекология. 2016; 6: 5-10. http://dx.doi.org/10.18565/aig.2016.6.5-10 [Serov V.N., Kan N.E., Tyutyunnik V.L. Prognostic value of a ratio of soluble fms-like tyrokinase1 to placental growth factor in pregnant women with preeclampsia. Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2016; (6): 5-10. (in Russian). http://dx.doi.org/10.18565/aig.2016.6.5-10]
2. Ходжаева З.С., Коган Е.А., Клименченко Н.И., Акатьева А.С., Сафонова А.Д., Холин А.М., Вавина О.В., Сухих Г.Т. Клинико-патогенетические особенности ранней и поздней преэклампсии. Акушерство и гинекология. 2015; 1: 12-7. [Khodzhaeva Z.S., Kogan E.A., Klimenchenko N.I., Akatyeva A.S., Kholin A.M., Vavina O.V., Sukhikh G.T. Clinical and pathogenetic features of early and late preeclampsia. Akusherstvo i ginekologiya/Obstetrics and Gynecology. 2015; 1: 12-7. (in Russian)]
3. Lamarca B. Endothelial dysfunction. An important mediator in the pathophysiology of hypertension during pre-eclampsia. Minerva Ginecol. 2012; 64(4): 309-20.
4. Reddy A., Suri S., Sargent I.L., Redman C.W., Muttukrishna S. Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia. PLoS One. 2009; 4(2): e4453.
5. Moore Simas T.A., Crawford S.L., Solitro M.J., Frost S.C., Meyer B.A., Maynard S.E. Angiogenic factors for the prediction of preeclampsia in high-risk women. Am. J. Obstet. Gynecol. 2007; 197(3): 244. e1-8.
6. Foidart Y.M., Schaaps Y.P., Chantraine F., Munaut C., Lorquet S. Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia – a step forward but not the definitive answer. J. Reprod. Immunol. 2009; 82(2): 106-11.
7. Kvehaugen A.S., Dechend R., Ramstad H.B., Troisi R., Fugelseth D., Staff A.C. Endothelial function and circulating biomarkers are disturbed in women and children after preeclampsia. Hypertension. 2011; 58(1): 63-9.
8. Иванец Т.Ю., Алексеева М.Л., Кан Н.Е., Тютюнник В.Л., Амирасланов Э.Ю., Насонова Д.М., Фанченко Н.Д. Диагностическая значимость определения плацентарного фактора роста и растворимой fms-подобной тирозинкиназы-1 в качестве маркеров преэклампсии. Проблемы репродукции. 2015; 21(4): 129-33. [Ivanets T.Yu., Alekseeva M.L., Kan N.E., Tyutyunnik V.L., Amiraslanov E.Yu., Nasonova D.M., Fanchenko N.D. Diagnostic significance of the determination of placental growth factor and soluble fms-like tyrosine kinase-1 as markers of pre-eclampsia. Problemy reproduktsii. 2015; 21(4): 129-33. (in Russian)]
9. Staff A.C. Circulating predictive biomarkers in preeclampsia. Pregnancy Hypertens. 2011; 1(1): 28-42.
10. Vatten L.J., Eskild A., Nilsen T.I., Jeansson S., Jenum P.A., Staff A.C. Changes in circulating level of angiogenic factors from the first to second trimester as predictors of preeclampsia. Am. J. Obstet. Gynecol. 2007; 196(3): 239-46.
11. Wang A., Rana S., Karumanchi S.A. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda). 2009; 24: 147-58.
12. Levine R.J., Maynard S.E., Qian C., Lim K.H., England L.J., Yu K.F. et al. Circulating angiogenic factors and the risk of preeclampsia. N. Engl. J. Med. 2004; 350(7): 672-83.
13. Wikström A.K., Larsson A., Eriksson U.J., Nash P., Nordén-Lindeberg S., Olovsson M. Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia. Obstet. Gynecol. 2007; 109(6):1368-74.
14. Verlohren S., Herraiz I., Lapaire O., Schlembach D., Moertl M., Zeisler H. et al. The sFlt-1/PlGF radio in different types of hypertensive pregnancy disorders and its prognostic potential in peeclamptic patients. Am. J. Obstet. Gynecol. 2012; 206(1): 58: e1-8.
15. Jelliffe-Pawlowski L.L., Shaw G.M., Currier R.J., Stevenson D.K., Baer R.J., O’Brodovich H.M., Gould J.B. Association of early preterm birth with abnormal levels of rutinely collected ferst- and second-thrimester biomarkers. Am. J. Obstet. Gynecol. 2013; 208(6): 492. e1-11.
16. Husse S., Gottschlich A., Schrey S., Stepan H., Hoffmann J. Predictive value of the sFlt1/PlGF ratio for the diagnosis of preeclampsia in high-risk patients. Z. Geburtshilfe Neonatol. 2014; 218(1): 34-41.
Received 09.06.2017
Accepted 23.06.2017
About the Authors
Ivanets Tatiana Yu., the head of the clinical laboratory, Research Center of Obstetrics, Gynecology and Perinatology Ministry of Health of Russia.117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79104042669. E-mail:t_ivanets@oparina4.ru.
Kan Natalia E., PhD, MD, the head of the obstetric department, Research Center of Obstetrics, Gynecology and Perinatology Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79262208655. E-mail: kan-med@mail.ru. Researcher ID B-2370-2015. ORCID ID 0000-0001-5087-5946
Tyutyunnik Victor L., PhD, MD, the head of the obstetric physiological department, Research Center of Obstetrics, Gynecology and Perinatology Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79039695041. E-mail: tioutiounnik@mail.ru. Researcher ID B-2364-2015.ORCID ID 0000-0002-5830-5099
Bezzubenko Yulia V., doctor for clinical laboratory diagnostics of the clinical laboratory, Research Center of Obstetrics, Gynecology and Perinatology
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79266077007. E-mail: j_bezzubenko@mail.ru
Ibragimov Ruslan R., specialist in automated systems of protection, Research Center of Obstetrics, Gynecology and Perinatology Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79852259181. E-mail: r_ibragimov@oparina4.ru
For citations: Ivanets T.Yu., Kan N.E., Tyutyunnik V.L., Bezzubenko Yu.V., Ibragimov R.R.
The role of the soluble fms-like tyrosin kinase-1 / the placental growth factor ratio
in the diagnostics of preeclampsia in physiological pregnancy and pregnancy after IVF.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (3): 37-42. (in Russian)
https://dx.doi.org/10.18565/aig.2018.3.37-42
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