Startseite Is there any role of interleukin-6 and high sensitive C-reactive protein in predicting IVF/ICSI success? A prospective cohort study
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Is there any role of interleukin-6 and high sensitive C-reactive protein in predicting IVF/ICSI success? A prospective cohort study

  • A. Seval Ozgu-Erdinc ORCID logo EMAIL logo , Ilay Gozukara , Serkan Kahyaoglu , Saynur Yilmaz , Omer Hamit Yumusak , Nafiye Yilmaz , Salim Erkaya und Yaprak Engin-Ustun
Veröffentlicht/Copyright: 26. November 2021
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Hormone Molecular Biology and Clinical Investigation
Aus der Zeitschrift Hormone Molecular Biology and Clinical Investigation Band 43 Heft 1

Abstract

Objectives

Studies have established a relationship between proinflammatory factors and implantation failure in IVF/ICSI cycles. Likewise, low-grade chronic inflammation is generally blamed for predisposing infertility. In the present study, we aimed to find a relationship between serum IL-6 and hs-CRP levels and IVF/ICSI cycle outcomes.

Methods

A total of 129 patients who consented to participate and attended the IVF unit of our department for the treatment of infertility have been enrolled in this prospective cohort study. Serum levels of high sensitive C-reactive protein and interleukin 6 have been detected at the beginning of the IVF/ICSI ovulation induction cycle. Cycle outcomes have been compared between patients with and without clinical pregnancy achievement following ART treatments. IVF/ICSI cycle outcomes of these two groups were also comparable except the number of >14 mm follicles, retrieved oocytes, metaphase II oocytes, and fertilized oocytes (2 pronuclei) which were in favor of the clinical pregnancy group.

Results

Mean serum hs-CRP levels were 3.08 mg/L (0.12–35.04) and 2.28 mg/L (0.09–22.52) patients with and without clinical pregnancy respectively. Mean serum IL-6 levels were 2 pg/mL (1–10.2) and 2 pg/mL (1–76.9) patients with and without clinical pregnancy respectively. Both tests were found to be statistically insignificant in predicting the success of the ART cycle in terms of implantation, clinical pregnancy, miscarriage, and live birth.

Conclusions

In the present study, we have not found any significant effect of hs-CRP and IL-6 levels in the IVF cycle. However, in the light of this and previous studies, large-scale research may prove the exact influence of these markers on IVF success.

Highlights

  1. There is an equilibrium between pro-and anti-inflammatory factors during the regulation of reproduction.

  2. Chronic low-grade inflammation has been found to be present in many reproductive dysfunctions.

  3. However in the present study we have not found any significant effect of hs-CRP and IL-6 levels in IVF cycle.

Keywords: ART; C-reactive protein; cytokines; immunology; interleukin-6; pregnancy
Corresponding author: Assoc. Prof. Dr. A. Seval Ozgu-Erdinc, University of Health Sciences, Ankara City Hospital, Bilkent, 06800, Ankara, Turkey, E-mail:

Acknowledgments

Preliminary results of this study is presented as a poster in the IV. Biannual Meeting of the Society of Reproductive Medicine and Surgery Congress, 26–29 September 2013 Belek, Antalya/Turkey.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Institutional Review Board approved the study (27/5/2013 #40).

References

1. Daney de Marcillac, F, Pinton, A, Guillaume, A, Sagot, P, Pirrello, O, Rongieres, C. What are the likely IVF/ICSI outcomes if there is a discrepancy between serum AMH and FSH levels? A multicenter retrospective study. J Gynecol Obstet Hum Reprod 2017;46:629–35. https://doi.org/10.1016/j.jogoh.2017.08.001.Suche in Google Scholar PubMed

2. Kahyaoglu, I, Dogru, HY, Aksakal, SE, Kaplanoglu, I, Dilbaz, S, Mollamahmutoglu, L. The effect of elevated basal follicle stimulating hormone levels on assisted reproductive technology cycle outcomes. Gynecol Obstet Reprod Med 2021;27:138–42. https://doi.org/10.21613/gorm.2019.998.Suche in Google Scholar

3. Necula, D, Gmuer, A, Mathis, J. The impact of endometriosis on the outcome of assisted reproductive techniques: role of fertility preservation. Horm Mol Biol Clin Investig 2021. https://doi.org/10.1515/hmbci-2020-0082.Suche in Google Scholar PubMed

4. Norwitz, ER, Schust, DJ, Fisher, SJ. Implantation and the survival of early pregnancy. N Engl J Med 2001;345:1400–8. https://doi.org/10.1056/nejmra000763.Suche in Google Scholar

5. Rubod, C, Fouquet, A, Bartolo, S, Lepage, J, Capelle, A, Lefebvre, C, et al.. Factors associated with pregnancy after in vitro fertilization in infertile patients with posterior deep pelvic endometriosis: a retrospective study. J Gynecol Obstet Hum Reprod 2019;48:235–9. https://doi.org/10.1016/j.jogoh.2018.06.002.Suche in Google Scholar PubMed

6. Elgun, T, Karacan, M, Sandal, AI, Irez, T. Can serum anti-mullerian hormone level and LH/FSH ratio be predictive of clinical pregnancy through intracytoplasmic sperm injection – embryo transfer? Gynecol Obstet Reprod Med 2020;26:25–30. https://doi.org/10.21613/gorm.2018.897.Suche in Google Scholar

7. Adashi, EY. The potential relevance of cytokines to ovarian physiology: the emerging role of resident ovarian cells of the white blood cell series. Endocr Rev 1990;11:454–64. https://doi.org/10.1210/edrv-11-3-454.Suche in Google Scholar PubMed

8. Trombly, DJ, Woodruff, TK, Mayo, KE. Roles for transforming growth factor beta superfamily proteins in early folliculogenesis. Semin Reprod Med 2009;27:14–23. https://doi.org/10.1055/s-0028-1108006.Suche in Google Scholar PubMed PubMed Central

9. Kayisli, UA, Guzeloglu-Kayisli, O, Arici, A. Endocrine-immune interactions in human endometrium. Ann N Y Acad Sci 2004;1034:50–63. https://doi.org/10.1196/annals.1335.005.Suche in Google Scholar PubMed

10. Kishimoto, T. Interleukin-6: from basic science to medicine – 40 years in immunology. Annu Rev Immunol 2005;23:1–21. https://doi.org/10.1146/annurev.immunol.23.021704.115806.Suche in Google Scholar PubMed

11. Tabibzadeh, S, Kong, QF, Babaknia, A, May, LT. Progressive rise in the expression of interleukin-6 in human endometrium during menstrual cycle is initiated during the implantation window. Hum Reprod 1995;10:2793–9. https://doi.org/10.1093/oxfordjournals.humrep.a135793.Suche in Google Scholar PubMed

12. Salmassi, A, Lu, S, Hedderich, J, Oettinghaus, C, Jonat, W, Mettler, L. Interaction of interleukin-6 on human granulosa cell steroid secretion. J Endocrinol 2001;170:471–8. https://doi.org/10.1677/joe.0.1700471.Suche in Google Scholar PubMed

13. Machelon, V, Emilie, D, Lefevre, A, Nome, F, Durand-Gasselin, I, Testart, J. Interleukin-6 biosynthesis in human preovulatory follicles: some of its potential roles at ovulation. J Clin Endocrinol Metab 1994;79:633–42. https://doi.org/10.1210/jcem.79.2.7519193.Suche in Google Scholar PubMed

14. Younis, A, Hawkins, K, Mahini, H, Butler, W, Garelnabi, M. 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 2014;31:1445–51. https://doi.org/10.1007/s10815-014-0237-9.Suche in Google Scholar PubMed PubMed Central

15. Oz, M, Polat, B, Ozgu, E, Seckin, KD, Tasin, C, Danisman, N. Interleukin-6 and C-reactive protein levels in the amniotic fluid as indicators of preterm delivery in Turkish women. Clin Exp Obstet Gynecol 2015;42:801–4.10.12891/ceog2009.2015Suche in Google Scholar

16. Ozgu-Erdinc, AS, Cavkaytar, S, Aktulay, A, Buyukkagnici, U, Erkaya, S, Danisman, N. Mid-trimester maternal serum and amniotic fluid biomarkers for the prediction of preterm delivery and intrauterine growth retardation. J Obstet Gynaecol Res 2014;40:1540–6. https://doi.org/10.1111/jog.12371.Suche in Google Scholar PubMed

17. Aslan Patlakoğlu, E, Altinkaya, SÖ, Uğur, M, Taşın, C, Kadıoğlu, N. Levels of IL-6 and IL-1β in umbilical cord blood in relation to mode of birth. Gynecol Obstet Reprod Med 2016;20:5–9.Suche in Google Scholar

18. Yi, L, Lilan, L, Haibo, Z. Changes of cytokines levels in peritoneal fluids of patients with endometriosis and its effect on reproductive activity. J Tongji Med Univ 2000;20:163–5. https://doi.org/10.1007/bf02887062.Suche in Google Scholar PubMed

19. Pepys, MB, Hirschfield, GM. C-reactive protein: a critical update. J Clin Invest 2003;111:1805–12. https://doi.org/10.1172/jci200318921.Suche in Google Scholar

20. Lacut, K, Oger, E, Le Gal, G, Blouch, MT, Abgrall, JF, Kerlan, V, et al.. Differential effects of oral and transdermal postmenopausal estrogen replacement therapies on C-reactive protein. Thromb Haemost 2003;90:124–31.10.1055/s-0037-1613608Suche in Google Scholar

21. Bassuk, SS, Rifai, N, Ridker, PM. High-sensitivity C-reactive protein: clinical importance. Curr Probl Cardiol 2004;29:439–93. https://doi.org/10.1016/s0146-2806(04)00074-x.Suche in Google Scholar

22. Ozkan, ZS, Deveci, D, Kumbak, B, Simsek, M, Ilhan, F, Sekercioglu, S, et al.. What is the impact of Th1/Th2 ratio, SOCS3, IL17, and IL35 levels in unexplained infertility? J Reprod Immunol 2014;103:53–8. https://doi.org/10.1016/j.jri.2013.11.002.Suche in Google Scholar PubMed

23. Devranoglu, B, Yayla Abide, C, Ozkaya, E, Senol, T, Kutlu, T, Kayatas Eser, S. Coagulation tests at trigger day in patients with Factor V Leiden Mutation to predict implantation failure. Gynecol Obstet Reprod Med 2018;24:76–81. https://doi.org/10.21613/gorm.2017.754.Suche in Google Scholar

24. An, LF, Zhang, XH, Sun, XT, Zhao, LH, Li, S, Wang, WH. 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 2015;44:164–73. https://doi.org/10.3109/08820139.2014.932377.Suche in Google Scholar PubMed

25. Üstüner, I, Sönmezer, M, Atabekoğlu, C, Ergun, A, Güllü, S, Aytaç, R. Chronic inflammation in women with polycystic ovarian syndrome. Gynecol Obstet Reprod Med 2006;12:180–5.Suche in Google Scholar

26. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Med Assoc 2013;310:2191–4.10.1001/jama.2013.281053Suche in Google Scholar PubMed

27. Meier-Ewert, HK, Ridker, PM, Rifai, N, Price, N, Dinges, DF, Mullington, JM. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem 2001;47:426–30. https://doi.org/10.1093/clinchem/47.3.426.Suche in Google Scholar

28. Almagor, M, Hazav, A, Yaffe, H. The levels of C-reactive protein in women treated by IVF. Hum Reprod 2004;19:104–6. https://doi.org/10.1093/humrep/deh036.Suche in Google Scholar PubMed

29. Orvieto, R, Chen, R, Ashkenazi, J, Ben-Haroush, A, Bar, J, Fisch, B. C-reactive protein levels in patients undergoing controlled ovarian hyperstimulation for IVF cycle. Hum Reprod 2004;19:357–9. https://doi.org/10.1093/humrep/deh089.Suche in Google Scholar PubMed

30. Levin, I, Gamzu, R, Mashiach, R, Lessing, JB, Amit, A, Almog, B. Higher C-reactive protein levels during IVF stimulation are associated with ART failure. J Reprod Immunol 2007;75:141–4. https://doi.org/10.1016/j.jri.2007.03.004.Suche in Google Scholar PubMed

31. Lindhard, A, Bentin-Ley, U, Ravn, V, Islin, H, Hviid, T, Rex, S, et al.. Biochemical evaluation of endometrial function at the time of implantation. Fertil Steril 2002;78:221–33. https://doi.org/10.1016/s0015-0282(02)03240-5.Suche in Google Scholar PubMed

32. Sacks, GP, Seyani, L, Lavery, S, Trew, G. Maternal C-reactive protein levels are raised at 4 weeks gestation. Hum Reprod 2004;19:1025–30. https://doi.org/10.1093/humrep/deh179.Suche in Google Scholar PubMed

33. Diba-Bagtash, F, Farshbaf-Khalili, A, Ghasemzadeh, A, Lotz, L, Fattahi, A, Shahnazi, M, et al.. Maternal C-reactive protein and in vitro fertilization (IVF) cycles. J Assist Reprod Genet 2020;37:2635–41. https://doi.org/10.1007/s10815-020-01924-1.Suche in Google Scholar PubMed PubMed Central

34. Blitek, A, Morawska, E, Ziecik, AJ. Regulation of expression and role of leukemia inhibitory factor and interleukin-6 in the uterus of early pregnant pigs. Theriogenology 2012;78:951–64. https://doi.org/10.1016/j.theriogenology.2012.05.016.Suche in Google Scholar PubMed

35. Prins, JR, Gomez-Lopez, N, Robertson, SA. Interleukin-6 in pregnancy and gestational disorders. J Reprod Immunol 2012;95:1–14. https://doi.org/10.1016/j.jri.2012.05.004.Suche in Google Scholar PubMed

36. Zenclussen, AC, Blois, S, Stumpo, R, Olmos, S, Arias, K, Malan Borel, I, et al.. Murine abortion is associated with enhanced interleukin-6 levels at the feto-maternal interface. Cytokine 2003;24:150–60. https://doi.org/10.1016/j.cyto.2003.08.002.Suche in Google Scholar PubMed

37. Altun, T, Jindal, S, Greenseid, K, Shu, J, Pal, L. Low follicular fluid IL-6 levels in IVF patients are associated with increased likelihood of clinical pregnancy. J Assist Reprod Genet 2011;28:245–51. https://doi.org/10.1007/s10815-010-9502-8.Suche in Google Scholar PubMed PubMed Central

38. Rehman, R, Ashraf, M, Jasmine, A, Lal, K, Alam, F. Cytokines and endometrial receptivity after intracytoplasmic sperm injection – a cohort study at Islamabad. J Pak Med Assoc 2018;68:862–6.Suche in Google Scholar

39. Deura, I, Harada, T, Taniguchi, F, Iwabe, T, Izawa, M, Terakawa, N. Reduction of estrogen production by interleukin-6 in a human granulosa tumor cell line may have implications for endometriosis-associated infertility. Fertil Steril 2005;83(Suppl 1):1086–92. https://doi.org/10.1016/j.fertnstert.2004.12.014.Suche in Google Scholar PubMed

40. Pennica, D, Shaw, KJ, Swanson, TA, Moore, MW, Shelton, DL, Zioncheck, KA, et al.. Cardiotrophin-1. Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex. J Biol Chem 1995;270:10915–22. https://doi.org/10.1074/jbc.270.18.10915.Suche in Google Scholar PubMed

41. Makkar, G, Ng, EH, Yeung, WS, Ho, PC. Reduced expression of interleukin-11 and interleukin-6 in the periimplantation endometrium of excessive ovarian responders during in vitro fertilization treatment. J Clin Endocrinol Metab 2006;91:3181–8. https://doi.org/10.1210/jc.2006-0180.Suche in Google Scholar PubMed

42. Seekford, ZK, Wooldridge, LK, Dias, NW, Timlin, CL, Sales, AF, Speckhart, SL, et al.. Interleukin-6 supplementation improves post-transfer embryonic and fetal development of in vitro-produced bovine embryos. Theriogenology 2021;170:15–22. https://doi.org/10.1016/j.theriogenology.2021.04.004.Suche in Google Scholar PubMed

43. Yang, J, Yang, X, Yang, H, Bai, Y, Zha, H, Jiang, F, et al.. Interleukin 6 in follicular fluid reduces embryo fragmentation and improves the clinical pregnancy rate. J Assist Reprod Genet 2020;37:1171–6. https://doi.org/10.1007/s10815-020-01737-2.Suche in Google Scholar PubMed PubMed Central

44. Wilczynski, JR. Th1/Th2 cytokines balance – yin and yang of reproductive immunology. Eur J Obstet Gynecol Reprod Biol 2005;122:136–43.10.1016/j.ejogrb.2005.03.008Suche in Google Scholar PubMed

45. Haddad, EK, Duclos, AJ, Antecka, E, Lapp, WS, Baines, MG. Role of interferon-gamma in the priming of decidual macrophages for nitric oxide production and early pregnancy loss. Cell Immunol 1997;181:68–75. https://doi.org/10.1006/cimm.1997.1199.Suche in Google Scholar PubMed

46. Otun, HA, Lash, GE, Innes, BA, Bulmer, JN, Naruse, K, Hannon, T, et al.. Effect of tumour necrosis factor-alpha in combination with interferon-gamma on first trimester extravillous trophoblast invasion. J Reprod Immunol 2011;88:1–11. https://doi.org/10.1016/j.jri.2010.10.003.Suche in Google Scholar PubMed

Received: 2021-05-11
Accepted: 2021-11-10
Published Online: 2021-11-26

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Letter to the Editor
  3. Is COVID-19 gender biased?
  4. Opinion Paper
  5. The probable mechanism of reduced androgen level in COVID-19 patients
  6. Original Articles
  7. Effect of Auraptene on angiogenesis in Xenograft model of breast cancer
  8. Zingiber officinale (Ginger) hydroalcoholic extract improved avoidance memory in rat model of streptozotocin-induced diabetes by regulating brain oxidative stress
  9. Role of N-terminal pro-B-type natriuretic peptide and troponin T in predicting right ventricular recovery in myocardial infarction
  10. Is there any role of interleukin-6 and high sensitive C-reactive protein in predicting IVF/ICSI success? A prospective cohort study
  11. Does serum TSH level act as a surrogate marker for psychological stress and cardio-metabolic risk among adolescent and young people?
  12. The effects of thyroid dysfunction on DNA damage and apoptosis in liver and heart tissues of rats
  13. The serum levels of testosterone in coronary artery disease patients; relation to NO, eNOS, endothelin-1, and disease severity
  14. Interaction of high-intensity endurance exercise and nandrolone on cardiac remodeling: role of adipo-cardiac axis
  15. Psoralidin exerts anti-tumor, anti-angiogenic, and immunostimulatory activities in 4T1 tumor‐bearing balb/c mice
  16. Short Communication
  17. COVID-19 pandemic and potential of artificial intelligence
  18. Case Report
  19. A positive urine pregnancy test with haemoperitoneum: misdiagnosed postpartum choriocarcinoma with uterine rupture mimicking ruptured ectopic pregnancy
  20. Review Articles
  21. COVID 19 vaccine in patients of hypercoagulable disorders: a clinical perspective
  22. Synopsis of symptoms of COVID-19 during second wave of the pandemic in India
  23. Clustered regularly interspaced short palindromic repeats, a glimpse – impacts in molecular biology, trends and highlights
https://doi.org/10.1515/hmbci-2021-0039
Schlagwörter für diesen Artikel
ART; C-reactive protein; cytokines; immunology; interleukin-6; pregnancy

Artikel in diesem Heft

  1. Frontmatter
  2. Letter to the Editor
  3. Is COVID-19 gender biased?
  4. Opinion Paper
  5. The probable mechanism of reduced androgen level in COVID-19 patients
  6. Original Articles
  7. Effect of Auraptene on angiogenesis in Xenograft model of breast cancer
  8. Zingiber officinale (Ginger) hydroalcoholic extract improved avoidance memory in rat model of streptozotocin-induced diabetes by regulating brain oxidative stress
  9. Role of N-terminal pro-B-type natriuretic peptide and troponin T in predicting right ventricular recovery in myocardial infarction
  10. Is there any role of interleukin-6 and high sensitive C-reactive protein in predicting IVF/ICSI success? A prospective cohort study
  11. Does serum TSH level act as a surrogate marker for psychological stress and cardio-metabolic risk among adolescent and young people?
  12. The effects of thyroid dysfunction on DNA damage and apoptosis in liver and heart tissues of rats
  13. The serum levels of testosterone in coronary artery disease patients; relation to NO, eNOS, endothelin-1, and disease severity
  14. Interaction of high-intensity endurance exercise and nandrolone on cardiac remodeling: role of adipo-cardiac axis
  15. Psoralidin exerts anti-tumor, anti-angiogenic, and immunostimulatory activities in 4T1 tumor‐bearing balb/c mice
  16. Short Communication
  17. COVID-19 pandemic and potential of artificial intelligence
  18. Case Report
  19. A positive urine pregnancy test with haemoperitoneum: misdiagnosed postpartum choriocarcinoma with uterine rupture mimicking ruptured ectopic pregnancy
  20. Review Articles
  21. COVID 19 vaccine in patients of hypercoagulable disorders: a clinical perspective
  22. Synopsis of symptoms of COVID-19 during second wave of the pandemic in India
  23. Clustered regularly interspaced short palindromic repeats, a glimpse – impacts in molecular biology, trends and highlights
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