THE ROLE OF VASCULAR HOMEOSTASIS IN WOMEN WITH INFERTILITY TREATED WITH ASSISTED REPRODUCTIVE TECHNOLOGIES AND WITH CONCOMITANT INTRAHEPATIC CHOLESTASIS

Oleksandra Hryhorivna Boichuk; Svitlana Mykolaivna Heryak; Stefan Volodymyrovych Khmil; Mariya Stefanivna Khmil

doi:10.31435/rsglobal_ws/28022021/7442

Oleksandra Hryhorivna Boichuk MD, professor at the Subdepartment of Obstetrics and Gynecology of the Department of Postgraduate Studies of Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine https://orcid.org/0000-0003-4439-3099
Svitlana Mykolaivna Heryak MD, PhD, DSc, Professor, The Head of the Department of Obstetrics and Gynecology No.2, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
Stefan Volodymyrovych Khmil MD, PhD, DSc, Professor, Department of Obstetrics and Gynecology No.2, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine, owner Medical Center “Сlinic of Prof. Stefan Khmil”, Ternopil, Ukraine
Mariya Stefanivna Khmil PhD, CEO Medical Center “Сlinic of Prof. Stefan Khmil”, Ternopil, Ukraine

DOI: https://doi.org/10.31435/rsglobal_ws/28022021/7442

Keywords: pregnancy, intrahepatic cholestasis, endothelium, infertility, ART

Abstract

Intrahepatic cholestasis of pregnancy (idiopathic jaundice of pregnancy, recurrent familial jaundice of pregnancy) is a benign familial disease manifesting itself in the gestational period in itching and (or) jaundice. As a rule, the disease is observed in the 3rd trimester of pregnancy, that is in the 28th-30th week, and may disappear by itself a few days after labor and recur during future pregnancies.
The aim of this research is to study the role and factors of vascular homeostasis regulation in women with infertility treated with assisted reproductive technologies (ART) and with concomitant intrahepatic cholestasis.
Intrahepatic cholestasis is characterized by the damage of endothelial cells of hepatic sinusoids, changes in the intrahepatic hemodynamics, increased production of cytokines and free radicals. The processes of angiogenesis in the liver are also closely connected with the functional capacity of endothelium. The L-arginine level in blood was measured using the photometric method based. The homocysteine level was measured by the enzymatic cycling method. To measure the level of placental growth factor (PGF) in blood plasma samples, we used the immunochemical method.
The research has found especially severe complications in the course of pregnancy after ART in those women with intrahepatic cholestasis whose placentas developed under the conditions of endothelial dysfunction from the very beginning of pregnancy.
So, these factors may be early prognostic markers of severe obstetrical and perinatal disorders in women with induced pregnancy and hepatobiliary disorders.

References

Pusl Т, Beuers U. Intrahepatic cholestasis of pregnancy. Orphanet J. Rare Dis. 2007; 2:26.

Zecca E. Intrahepatic cholestasis of pregnancy and neonatal respiratory distress syndrome. Pediatrics. 2006; 117:1669-1672.

Germain AM, Carvajal JA, Glasinovic JC, et al. Intrahepatic cholestasis of pregnancy: an intriguing pregnancy-specific disorder. J. Soc. Gynecol. Investig. 2002; 9:10-14.

Lammert F, Marschall HU, Glantz A, Matern S. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J. Hepatol. 2000; 33:1012-1021.

Fagan EA. Intrahepatic cholestasis of pregnancy. Clin Liver Dis. 2002; 3:603-632.

Diaferia A, Nicastri P, Tartagni M, et al. Ursodeoxycholic acid in pregnant women with cholestasis. Obstet. Gynecol. 1999; 52:133-140.

Roponen A. Intrahepatic cholestasis of pregnancy genetic background, epidemiology and hepatobiliary consequences. Academic Dissertation. Helsinki University Central Hospital, 2006.

Bacq Y, Sentilhes L, Reyes HB, et al. Efficacy of Ursodeoxycholic Acid in Treating Intrahepatic Cholestasis of Pregnancy: A Metaanalysis. Gastroenterology. 2012; 143;6:1492-1501.

Pauli-Magnus C, Meier PJ, Stieger B. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy. Semin. Liver Dis. 2010; 30;2:147-159.

Fagan EA. Intrahepatic cholestasis of pregnancy. Clin. Liver Dis. 2002; 3:603-632.

Reyes H, Sjövall J. Bile acids and progesterone metabolites in intrahepatic cholestasis of pregnancy. Ann. Med. 2003; 32;2:94-106.

Shekhtman ММ. Manual on extragenital pathology in pregnant women. Мoscow. 1999.

Painter JN, Savander M, Ropponen A, et al. Sequence variation in the ATP8B1 gene and intrahepatic cholestasis of pregnancy. Eur. J. Hum. Genet. 2005; 13:435-439.

Paternoster DM, Fabris F, Palu G, et al. Intra-hepatic cholestasis of pregnancy in hepatitis C virus infection. Acta Obstet. Gynecol. Scand. 2002; 81:99-103.

Wikström Shemer E, Marschall HU. Decreased 1,25-dihydroxy vitamin D levels in women with intrahepatic cholestasis of pregnancy. Acta Obstet. Gynecol. Scand. 2010; 89;11:1420-1423.

Grigoryev PY, Yakovenko YP. Intrahepatic cholestasis with liver diseases: from diagnosis to treatment. Lechashchiy Vrach. 1999; 6:14-17.

Beuers U, Pusl T. Intrahepatic cholestasis of pregnancy - a heterogeneous group of pregnancy-related disorders? Hepatology. 2006; 43:647-649.

Nichols AA. Cholestasis of pregnancy: a review of the evidence. J. Perinat. Neonatal. Nurs. 2005; 19:217-225.

Mullally BA, Hansen WF. Intrahepatic cholestasis of pregnancy: review of the literature. Obstet. Gynecol. Surv. 2002; 57:47-52.

Riely CA, Bacq Y. Intrahepatic cholestasis of pregnancy. Clinics in Liver Disease. 2004; 8:167-176.

Ropponen A., Sund R., Riikonen S. et al. Intrahepatic cholestasis of pregnancy as an indicator of liver and biliary diseases: a population-based study. Hepatology. 2006;43:723-728.