Abstract
Purpose
Retrospective cohort studies have shown a relationship between maternal serum interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra) levels and in vitro fertilization (IVF) cycle outcome. The objective of this investigation was to explore the correlation between serum IL-1β and/or IL-1Ra levels obtained prospectively and IVF outcomes.
Methods
Sera from 205 women were collected just prior to initiation of their IVF cycle, at the time of human chorionic gonadotropin administration, day 24 of IVF cycle, day 28, and day 35. Sera were analyzed for IL-1β and IL-1Ra using commercially available ELISA kits. Cycle outcomes were followed prospectively. Data were analyzed using Friedman analysis of variance by ranks and chi-square analysis.
Results
Among women with a viable pregnancy, IL-1β serum levels increased over time for those that proceeded to deliver or had an ongoing pregnancy. There was no increase in serum levels for those with subsequent pregnancy loss. Of the women that had an embryo transfer, detectable IL-1β levels at the start of the cycle were associated with successful IVF outcome (p = 0.027). Of women with a positive pregnancy test, undetectable IL-1β at the start of the cycle were associated with subsequent pregnancy loss (p = 0.046). For all IL1-Ra serum analysis, there were no significant results.
Conclusions
The increasing levels of IL-1β over time are consistent with the known role of the IL-1 cytokine family in implantation and pregnancy. Additionally, we confirm in a prospective investigation the positive relationship between detectable serum IL-1β at the start of IVF cycle and outcome.
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References
Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2014 Assisted reproductive technology national summary report Atlanta, GA; 2016 Available from: http://www.cdc.gov/art/reports/.
Ghaebi M, Nouri M, Ghasemzadeh A, Farzadi L. Immune regulatory network in successful pregnancy and reproductive failures. Biomed Pharmacother. 2017;88:61–73.
Makrigiannakis A, Petsas G, Toth B, Relakis K. Recent advances in understanding immunology of reproductive failure. J Reprod Immunol. 2011;90:96–104.
Hyde KJ, Schust DJ. Immunologic challenges of human reproduction: an evolving story. Fertil Steril. 2016;106:499–510.
Ramhorst R, Grasso E, Paparini D, Hauk V, Calo G, Vota D, et al. Decoding the chemokine network that links leukocytes with decidual cells and the trophoblast during early implantation. Cell Adhes Migr. 2016;10:197–207.
Dekel N, Gnainsky Y, Granot I, Racicot K, Mor G. The role of inflammation for a successful implantation. Am J Reprod Immunol. 2014;72:141–7.
Granot I, Gnainsky Y, Dekel N. Endometrial inflammation and effect on implantation improvement and pregnancy outcome. Reproduction. 2012;144:661–8.
van de Veerdonk FL, Netea MG. New insights in the immunobiology of IL-1 family members. Front Immunol. 2013;4:1–11.
Simon C, Frances A, Piquette GN, el Danasouri I, Zurawski G, Dang W, et al. Embryonic implantation in mice is blocked by interleukin-1 receptor antagonist. Endocrinology. 1994;134:521–8.
Simon C, Mercader A, Gimeno MJ, Pellicer A. The interleukin-1 system and human implantation. Am J Reprod Immunol. 1997;37:64–72.
Irikura VM, Lagraoui M, Hirsh D. The epistatic interrelationships of IL-1, IL-1 receptor antagonist, and the type I IL-1 receptor. J Immunol. 2002;169:393–8.
Kruessel JS, Huang HY, Wen Y, Kloodt AR, Bielfeld P, Polan ML. Different pattern of interleukin-1beta-(IL-1beta), interleukin-1 receptor antagonist- (IL-1ra) and interleukin-1 receptor type I-(IL-1R tI) mRNA-expression in single preimplantation mouse embryos at various developmental stages. J Reprod Immunol. 1997;34:103–20.
Simon C, Frances A, Piquette G, Hendrickson M, Milki A, Polan ML. Interleukin-1 system in the materno-trophoblast unit in human implantation: immunohistochemical evidence for autocrine/paracrine function. J Clin Endocrinol Metab. 1994;78:847–54.
Simon C, Piquette GN, Frances A, Polan ML. Localization interleukin-1 type I receptor and interleukin-1b in human endometrium throughout menstrual cycle. J Clin Endocrinol Metab. 1993;77:549–55.
Spandorfer SDD, Neuer A, Liu H-CC, Bivis L, Clarke R, Veeck L, et al. Interleukin-1 levels in the supernatant of conditioned media of embryos grown in autologous endometrial coculture: correlation with outcome after in vitro fertilization. Am J Reprod Immunol. 2000;43:6–11.
Spandorfer SD, Neuer A, Liu HC, Rosenwaks Z, Witkin SS. Involvement of interleukin-1 and the interleukin-1 receptor antagonist in in vitro embryo development among women undergoing in vitro fertilization-embryo transfer. J Assist Reprod Genet. 2003;20:502–5.
Lekovich J, Witkin SS, Doulaveris G, Orfanelli T, Shulman B, Pereira N, et al. Elevated serum interleukin-1β levels and interleukin-1β-to-interleukin-1 receptor antagonist ratio 1 week after embryo transfer are associated with ectopic pregnancy. Fertil Steril. 2015;104:1190–4.
Fasouliotis SJ, Spandorfer SD, Schattman G, Liu HC, Roberts JE, Rosenwaks Z. Maternal serum levels of interferon-gamma and interleukin-2 soluble receptor-alpha predict the outcome of early IVF pregnancies. Hum Reprod. 2004;19:1357–63.
Huang H, Chan S, Sc B, Wu C. Interleukin-1 system messenger ribonucleic acid and protein expression in human fallopian tube may be associated with ectopic pregnancy. Fertil Steril. 2005;84:1484–92.
Spandorfer S, Avrech O, Colombero L, Palermo G, Rosenwaks Z. Effect of parental age on fertilization and pregnancy characteristics in couples treated by intracytoplasmic sperm injection. Hum Reprod. 1998;13:334–8.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Kreines, F.M., Nasioudis, D., Minis, E. et al. IL-1β predicts IVF outcome: a prospective study. J Assist Reprod Genet 35, 2031–2035 (2018). https://doi.org/10.1007/s10815-018-1296-0
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DOI: https://doi.org/10.1007/s10815-018-1296-0