Assessment Interleukins 3, 5 and 6 Concentration in Follicular Fluid and Their Diagnostic Value in Patients with Unexplained Infertility

Subject Areas :

mohmmad Ghodsi ¹ ( Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran. )
vida hojati ² ( Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran. )
armin atarzadeh ³ ( فلوشیپ پاتولوژی و سیتوژنتیک مولکولی، بیمارستان امام رضا، دانشگاه علوم پزشکی مشهد، مشهد، ایران. )
bita Saifi ⁴ ( Assistant Professor, Department of Anatomy, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran )

Received: 2019-10-17 Accepted : 2019-12-22 Published : 2019-12-22

Keywords:

Abstract :

Inroduction & Objective: Our aim a cross-sectional study was to compare the follicular fluid level of interleukins 3, 5, and 6 and clinical factors in patients with unexplained infertility with healthy subjects in the outcome of In vitro fertilization (IVF).  Material and Methods: Initiation of ovulation stimulating with ovulation stimulating drugs in different protocols started in 60 infertile patients with unexplained infertility and 40 fertile women. Subjects underwent antagonist and agonist protocol for ovarian stimulation.Then their follicular fluid was separated and the follicular concentration of interleukins 3, 5 and 6 determined by Enzyme-linked immunosorbent assay (ELISA) method. The diagnostic value of these 3 interleukins was also evaluated using the Roc curve. Results: Among the clinical factors, the endometrial thickness and testosterone levels significantly between the two groups (P <0.0001and P = 0.002), that the mean endometrial thickness was lower and the mean testosterone level was higher than the control group. So, hirsutism and hyperandrogenism significantly correlated between the patient and control groups (P = 0.046 and P = 0.046). Interleukin-3, 5, and 6 concentrations decreased in the patient, that the only reduction in IL-5 concentration significantly in the case group compared to the healthy group (P <0.0001). The diagnostic accuracy of IL-5 in the FF wasmoderate with the area under the curve (AUC) of 0.71. Conclusion: There is a significant difference in the follicular fluid interleukin-5 concentration between infertile and fertile women. This cytokine may be involved in the pathophysiology of unexplained infertility.

References:

1.Altun, T. (2011). Low follicular fluid IL-6 levels in IVF patients are associated with increased likelihood of clinical pregnancy. J Assist Reprod Genet, 28(3); 245-51.

2.An, L. F. (2015). Unexplained infertility patients have increased serum IL-2, IL-4, IL-6, IL-8, IL-21, TNFalpha, IFNgamma and increased Tfh/CD4 T cell ratio: increased Tfh and IL-21 strongly correlate with presence of autoantibodies. Immunol Invest, 44(2); 164-73.

3.Azad, M. (2017). T helper cell subsets and related cytokines in infertile women undergoing in vitro fertilization before and after seminal plasma exposure. Clin Exp Reprod Med, 44(4); 214-223.

4.Brandes, M. (2011). Unexplained infertility: overall ongoing pregnancy rate and mode of conception. Hum Reprod, 26(2); 360-8.

5.Broughton, S. E. (2015). The betac receptor family - Structural insights and their functional implications. Cytokine, 74(2); 247-58.

6.CbOkpalaji, B. (2016). Serum cytokine concentrations in infertile and fertile women. a preliminary study in port harcourt, nigeria. IOSR Journal of Dental and Medical Sciences, 15(09); 77-79.

7.Chan, K. J. (2018). Exogenous testosterone does not induce or exacerbate the metabolic features associated with pcos among transgender men. Endocr Pract, 24(6); 565-572.

8.Demir, B. (2009). Serum IL-6 level may have role in the pathophysiology of unexplained infertility. Am J Reprod Immunol, 62(4); 261-7.

9.Gillessen, S. (2001). Overlapping roles for granulocyte-macrophage colony-stimulating factor and interleukin-3 in eosinophil homeostasis and contact hypersensitivity. Blood, 97(4); 922-8.

10.Harry Hatasaka, MD. (2011). New perspectives for unexplained infertility. Clinical Obstetrics And Gynecology, 54(4); 727–733.

11.Kouro, T., Takatsu, K. (2009). IL-5- and eosinophil-mediated inflammation: from discovery to therapy. Int Immunol, 21(12); 1303-9.

12.Kritas, SK., Saggini, A., Cerulli, G., Caraffa, A., Antinolfi, P., Pantalone, A. (2014). Interrelationship between IL-3 and mast cells. Journal of Biological Regulators and Homeostatic Agents, 28(1); 17-21.

13.Lerchbaum, E. (2014). Hyperan drogenemia in polycystic ovary syndrome: exploration of the role of free testosterone and androstenedione in metabolic phenotype. PLoS One, 9(10); e108263.

14. Mutar, M. B. (2011). Role of some cytokines on reproduction. Middle East Fertility Society Journal, 16(3); 220-223.

15.Ray, A. (2012). Unexplained infertility: an update and review of practice. Reprod Biomed Online, 24(6); 591-602.

16.Sarapik, A. (2012). Follicular proinflammatory cytokines and chemokines as markers of IVF success. Clin Dev Immunol, 2012; 606459.

17.Sferruzzi-Perri, A., Robertson, N., S. A., L. A. (2003). Dent, interleukin-5 transgene expression and eosinophilia are associated with retarded mammary gland development in mice. Biol Reprod, 69(1); 224-33.

18.Shahin, A. Y. (2008). Endometrial sonographic characters predicting pregnancy following recurrent clomiphene induction in unexplained infertility. Reproductive BioMedicine, 17(6); 795-802.

19.Sorokin, Y. (2010). Maternal serum interleukin-6, C-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth <32 weeks and adverse neonatal outcomes. Am J Perinatol, 27(8); 631-40.

20.Sykes, L. (2012). Changes in the Th1:Th2 cytokine bias in pregnancy and the effects of the anti-inflammatory cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J2. Mediators Inflamm, 2012; 416739.

21.Sykes, L. (2012). The Th1:th2 dichotomy of pregnancy and preterm labour. Mediators Inflamm, 2012; 967629.

22.Vieira, A., Garra, O’, P. (2007). TH1 cells control themselves by producing interleukin-10. Nature Publishing Group, 7; 587-601.

23.Whitcomb, B. W. (2014). Urinary cytokine and chemokine profiles across the menstrual cycle in healthy reproductive-aged women. Fertil Steril, 101(5); 1383-91.

24.Younis, A. (2014). Serum tumor necrosis factor-alpha, interleukin-6, monocyte chemotactic protein-1 and paraoxonase-1 profiles in women with endometriosis, PCOS, or unexplained infertility. J Assist Reprod Genet, 31(11); 1445-51.

25.Zarko, S., Zvonimir, P. (2004). Effect increased testosterone level on women's fertility. Diabetologia Croatica, (3); 33-38