Effect of Dydrogesterone on the Outcome of Idiopathic Intrauterine Growth Restriction: A Double-blind Clinical Trial Study

Document Type : Original Article

Authors
Elaheh Zarean
Fatemeh Mostajeran
Zahra Dayani
Department of Obstetrics and Gynecology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Background: The aim of this study was to evaluate the effect of dydrogesterone in the outcome of idiopathic intrauterine growth restriction (IUGR). Materials and Methods: It is a double-blind randomized control clinical trial study that was done in Shahid Beheshti hospital of Isfahan during 2015–2016. In this study, 89 pregnant women with idiopathic IUGR fetus were selected and randomly divided into two intervention and control groups. Intervention group was treated with dydrogesterone 10 mg every 12 h for 2 weeks, while the control group received conventional management and treatment of IUGR, which also has been performed in the intervention group. Results: After 2 weeks of intervention, fetal weight was significantly increased in dydrogesterone group as compared to control group (2053.15 vs. 1736.36 g, P = 0.001); furthermore, we observed significant differences in the term of fetal abdominal circumference between the groups (27.25 vs. 25.92 cm, P = 0.006). Middle cerebral artery resistance index (0.67 vs. 0.83, P < 0.001) and uterine artery (UA) resistance index (0.68 vs. 0.81, P < 0.001) were significantly decreased in dydrogesterone group as compared to control group. Conclusions: Our results showed that dydrogesterone reduces resistance index of uterine artery and middle cerebral and increased fetal weight, while no sign of toxicity was observed. Dydrogesterone supplementation would have the potentiality to become a simple and economic means to prevent IUGR.

Keywords

1.
Garite TJ, Clark R, Thorp JA. Intrauterine growth restriction increases morbidity and mortality among premature neonates. Am J Obstet Gynecol 2004;191:481-7.  Back to cited text no. 1
[PUBMED]    
2.
Koukoura O, Sifakis S, Spandidos DA. DNA methylation in the human placenta and fetal growth (review). Mol Med Rep 2012;5:883-9.  Back to cited text no. 2
[PUBMED]    
3.
Romo A, Carceller R, Tobajas J. Intrauterine growth retardation (IUGR): Epidemiology and etiology. Pediatr Endocrinol Rev 2009;6 Suppl 3:332-6.  Back to cited text no. 3
[PUBMED]    
4.
Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon ES. Birth weight standards in the live-born population in Israel. Isr Med Assoc J 2005;7:311-4.  Back to cited text no. 4
[PUBMED]    
5.
Figueras F, Gratacós E. Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol. Fetal Diagn Ther 2014;36:86-98.  Back to cited text no. 5
    
6.
Chernausek SD. Update: Consequences of abnormal fetal growth. J Clin Endocrinol Metab 2012;97:689-95.  Back to cited text no. 6
[PUBMED]    
7.
Regev RH, Reichman B. Prematurity and intrauterine growth retardation – Double jeopardy? Clin Perinatol 2004;31:453-73.  Back to cited text no. 7
[PUBMED]    
8.
Wadhwa L, Batra S, Tempe A. Role of dydrogesterone in the treatment of idiopathic IUGR. Int J Reprod Contracept Obstet Gynecol 2013;2:157-60.  Back to cited text no. 8
    
9.
Martin CR. Prenatal diagnosis and treatment. Manual of Neonatal Surgical Intensive Care. Michigan: BC Decker; 2009. p. 238.  Back to cited text no. 9
    
10.
Bujold E, Roberge S, Lacasse Y, Bureau M, Audibert F, Marcoux S, et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: A meta-analysis. Obstet Gynecol 2010;116:402-14.  Back to cited text no. 10
[PUBMED]    
11.
Barclay L. Vaginal progesterone reduces risk of preterm birth. Am J Obstet Gynecol 2003;188:419-24.  Back to cited text no. 11
    
12.
Dosiou C, Hamilton AE, Pang Y, Overgaard MT, Tulac S, Dong J, et al. Expression of membrane progesterone receptors on human T lymphocytes and Jurkat cells and activation of G-proteins by progesterone. J Endocrinol 2008;196:67-77.  Back to cited text no. 12
[PUBMED]    
13.
Miller L, Hunt JS. Regulation of TNF-alpha production in activated mouse macrophages by progesterone. J Immunol 1998;160:5098-104.  Back to cited text no. 13
[PUBMED]    
14.
Paonessa DJ, Shields AD, Howard BC, Gotkin JL, Deering SH, Hoeldtke NJ, et al. 17-hydroxyprogesterone caproate reverses induced vasoconstriction of the fetoplacental arteries by the thromboxane mimetic U46619. Am J Obstet Gynecol 2006;195:1011-4.  Back to cited text no. 14
[PUBMED]    
15.
Li HF, Zheng TZ, Li W, Qu SY, Zhang CL. Effect of progesterone on the contractile response of isolated pulmonary artery in rabbits. Can J Physiol Pharmacol 2001;79:545-50.  Back to cited text no. 15
[PUBMED]    
16.
Cetingoz E, Cam C, Sakallı M, Karateke A, Celik C, Sancak A, et al. Progesterone effects on preterm birth in high-risk pregnancies: A randomized placebo-controlled trial. Arch Gynecol Obstet 2011;283:423-9.  Back to cited text no. 16
    
17.
Cianfarani S, Geremia C, Scott CD, Germani D. Growth, IGF system, and cortisol in children with intrauterine growth retardation: Is catch-up growth affected by reprogramming of the hypothalamic-pituitary-adrenal axis? Pediatr Res 2002;51:94-9.  Back to cited text no. 17
[PUBMED]    
18.
Hermenegildo C, Oviedo PJ, García-Martínez MC, García-Pérez MA, Tarín JJ, Cano A, et al. Progestogens stimulate prostacyclin production by human endothelial cells. Hum Reprod 2005;20:1554-61.  Back to cited text no. 18
    
19.
Jogee M, Myatt L, Elder MG. Decreased prostacyclin production by placental cells in culture from pregnancies complicated by fetal growth retardation. Br J Obstet Gynaecol 1983;90:247-50.  Back to cited text no. 19
[PUBMED]    
20.
Kaneoka T, Shimizu H, Matsuoka I, Taguchi S, Shirakawa K. Prenatal diagnosis and treatments of intrauterine growth retardation (author's transl). Nihon Sanka Fujinka Gakkai Zasshi 1982;34:233-42.  Back to cited text no. 20
[PUBMED]    
21.
Kaneoka T, Aso M, Nobori M, Aonuma M, Shimizu H, Shirakawa K, et al. Ultrasonic and biochemical detection and prenatal treatments of intra-uterine fetal growth retardation (author's transl). Nihon Sanka Fujinka Gakkai Zasshi 1980;32:103-12.  Back to cited text no. 21
    
22.
Banerjee S, Smallwood A, Moorhead J, Chambers AE, Papageorghiou A, Campbell S, et al. Placental expression of interferon-gamma (IFN-gamma) and its receptor IFN-gamma R2 fail to switch from early hypoxic to late normotensive development in preeclampsia. J Clin Endocrinol Metab 2005;90:944-52.  Back to cited text no. 22
[PUBMED]    
Advanced Biomedical Research
Volume 2018, june
June 2018
Pages 1-5