Prospective study to estimate the role of different infertility factors in prediction of unsuccessful IVF outcome

Authors

DOI:

https://doi.org/10.18370/2309-4117.2021.62.14-21

Keywords:

infertility, GroEl, heat shock protein HSP60, IVF, ELISA, implantation failure

Abstract

Research objective: in a prospective controlled study to investigate the role of HSP60, GroEl and other infertility factors as predictors of successful IVF outcome.
Materials and methods. 106 female patients were divided into two groups: 54 individuals who received conventional treatment for infertility (using ICSI techniques for IVF) and 52 individuals who received conventional therapy with intravenous IgG, enoxaparin and aspirin. All collected blood samples were tested for HSP60 and GroEl antibodies using immunofluorescence and ELISA techniques at the time of admission, after treatment (and before embryo transfer), and after embryo transfer. We analyzed the factors that can be helpful as prognostic parameters to estimate the risk of implantation failure.
Results. The risk of implantation failure is predicted when HSP60 level decreases from the first to the second measurement by less than 0.02 optical density units, with a sensitivity of 62% (95% confidence interval (CI) 47.2–75.3), and a specificity of 87.5% (95% CI 75.9–94.8), the positive predictive value was 81.6% (95% CI 68.2–90.2), the negative predictive value was 72.1% (95% CI 64.1–78.8). The GroEl value for the second dimension was more than 0.411 optical density units, which suggests a risk of treatment failure with a sensitivity of 64% (95% CI 49.2–77.1) and a specificity of 85.6% (95% CI 73.8–93.6), the positive predictive value was 80.0% (95% CI 67.1–88.7), the negative predictive value was 72.7% (95% CI 64.5–79.7). The highest (p < 0.05) value was observed at the beginning of treatment, and the lowest (p < 0.05) – during the third measurement.
Treatment of the underlying cause of infertility led to a decrease in HSP60 and GroEl levels, which ensured a positive in vitro fertilization result. It was found that HSP60 and GroEl have a strong association with embryo implantation. The risk of implantation failure was strongly associated with twelve factors, the area under the curve (AUC) was 0.85 (95% CI 0.76–0.91).
Conclusions. HSP60 and GroEl are good prognostic factors for predicting a successful IVF outcome in patients undergoing infertility treatment. The measurement of these parameters during the initial infertility examination may help in the immediate diagnosis of autoimmune infertility. Embryo implantation is a multifactorial process. The risk of implantation failure should be evaluated with multiple factors (twelve factors).

Author Biographies

V.O. Berestovyi, Institute of Postgraduate Education, O.O. Bogomolets National Medical University, Kyiv

Assistant, Department of Obstetrics, Gynecology and Neonatology

A. Mahmood, Institute of Postgraduate Education, O.O. Bogomolets National Medical University, Kyiv

Postgraduate student, Department of Obstetrics, Gynecology and Neonatology

A.M. Martych, Institute of Postgraduate Education, O.O. Bogomolets National Medical University, Kyiv

Postgraduate student, Department of Obstetrics, Gynecology and Neonatology

A.B. Prylutska, Institute of Postgraduate Education, O.O. Bogomolets National Medical University, Kyiv

PhD, assistant, Department of Obstetrics, Gynecology and Neonatology

O.O. Berestovyi, Reproductive Medicine Centre “Materi Clinic”, Kyiv

PhD, head of the Department Assisted Reproductive Technologies

D.O. Govsieiev, Institute of Postgraduate Education, O.O. Bogomolets National Medical University, Kyiv

MD, professor, head of the Department of Obstetrics, Gynecology and Neonatology

References

  1. Mascarenhas, M.N., Flaxman, S.R., Boerma, T., et al. “National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys.” PLoS Med 9.12 (2012): e1001356.
  2. Zegers-Hochschild, F., Adamson, G.D., de Mouzon, J., et al. “The international committee for monitoring assisted reproductive technology (ICMART) and the world health organization (WHO) revised glossary on ART terminology, 2009.” Hum Reprod 24.11 (2009): 2683–7.
  3. Crosignani, P., Collins, J., Cooke, I., et al. “Unexplained infertility (recommendation of ESHRE workshop).” Hum Reprod 8 (1993): 977–80.
  4. Gnoth, C., Godehardt, E., Frank-Herrmann, P., et al. “Definition and prevalence of subfertility and infertility.” Hum Reprod 20.5 (2005): 1144–7.
  5. Porcu-Buisson, G., Lambert, M., Lyonnet, L., et al. “Soluble MHC Class I chain-related molecule serum levels are predictive markers of implantation failure and successful term pregnancies following IVF.” Hum Reprod 22.8 (2007): 2261–6.
  6. dos Santos Silva, I., Wark, P., McCormack, V., et al. “Ovulation-stimulation drugs and cancer risks: a long-term follow-up of a British cohort.” Br J Cancer 100.11 (2009): 1824–31.
  7. Liat, L.-G., Jaron, R., Liraz, O., et al. “Are infertility treatments a potential risk factor for cancer development? Perspective of 30 years of follow-up.” Gynecol Endocrinol 28.10 (2012): 809–14.
  8. Yoshinaga, K. “Review of factors essential for blastocyst implantation for their modulating effects on the maternal immune system.” Semin Cell Dev Biol 19.2 (2008): 161–9.
  9. Hong, Y.H., Kim, S.J., Moon, K.Y., et al. “Impact of presence of antiphospholipid antibodies on in vitro fertilization outcome.” Obstet Gynecol Sci 61.3 (2018): 359.
  10. El Hasbani, G., Khamashta, M., Uthman, I. “Antiphospholipid syndrome and infertility.” Lupus 29.2 (2020): 105–17.
  11. Abdi, Z., Mohsenzadeh, S., Anarkooli, I.J., et al. “The effect of HSP60 on fertilization and pre-implantation embryo development in mice: an in vitro study.” Acta Endocrinol (Bucharest) 15.2 (2019): 153.
  12. Mekinian, A., Cohen, J., Alijotas-Reig, J., et al. “Unexplained recurrent miscarriage and recurrent implantation failure: is there a place for immunomodulation?” Am J Reprod Immunol 76.1 (2016): 8–28.
  13. Vitagliano, A., Saccardi, C., Litta, P.S., Noventa, M. “Chronic endometritis: really so relevant in repeated IVF failure?” Am J Reprod Immunol 78.6 (2017).
  14. Kushnir, V.A., Solouki, S., Sarig-Meth, T., et al. “Systemic inflammation and autoimmunity in women with chronic endometritis.” Am J Reprod Immunol 75.6 (2016): 672–7.
  15. Malizia, B.A., Hacker, M.R., Penzias, A.S. “Cumulative live-birth rates after in vitro fertilization.” N Engl J Med 360.3 (2009): 236–43.
  16. Shapiro, B.S., Richter, K.S., Harris, D.C., Daneshmand, S.T. “Dramatic declines in implantation and pregnancy rates in patients who undergo repeated cycles of in vitro fertilization with blastocyst transfer after one or more failed attempts.” Fertil Steril 76.3 (2001): 538–42.
  17. Westrom, L. “Chlamydia and its effect on reproduction.” J Br Fer Soc 1.1 (1996): 23–30.
  18. Coppus, S., Land, J., Opmeer, B.C., et al. “Chlamydia trachomatis IgG seropositivity is associated with lower natural conception rates in ovulatory subfertile women without visible tubal pathology.” Hum Reprod 26.11 (2011): 3061–7.
  19. Linhares, I.M., Witkin, S.S. “Immunopathogenic consequences of Chlamydia trachomatis 60 kDa heat shock protein expression in the female reproductive tract.” Cell Stress Chaperones 15.5 (2010): 467–73.
  20. Cates Jr, W., Wasserheit, J.N. “Genital chlamydial infections: epidemiology and reproductive sequelae.” Am J Obstet Gynecol 164.6 (1991): 1771–81.
  21. Dabekausen, Y.A., Evers, J.L., Land, J.A., Stals, F.S. “Chlamydia trachomatis antibody testing is more accurate than hysterosalpingography in predicting tubal factor infertility.” Fertil Steril 61.5 (1994): 833–7.
  22. Tsevat, D.G., Wiesenfeld, H.C., Parks, C., Peipert, J.F. “Sexually transmitted diseases and infertility.” Am J Obstet Gynecol 216.1 (2017): 1–9.
  23. Dalal, R. “Infection and Infertility.” Genital Infections and Infertility: IntechOpen (2016).
  24. Schuchardt, L., Rupp, J. “Chlamydia trachomatis as the cause of infectious infertility: acute, repetitive or persistent long-term infection?” Biology of Chlamydia. Springer (2016): 159–82.
  25. Muller, V., Savicheva, A., Kogan, I., et al. “Association between anti-chlamydial immunity and IVF outcome.” Gynecol Endocrinol 31.1 (2015): 69–73.
  26. Hoenderboom, B.M., van Benthem, B.H., van Bergen, J.E., et al. “Relation between Chlamydia trachomatis infection and pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility in a Dutch cohort of women previously tested for chlamydia in a chlamydia screening trial.” Sex Transm Infect 95.4 (2019): 300–6.
  27. Den Heijer, C.D., Hoebe, C.J., Driessen, J.H., et al. “Chlamydia trachomatis and the risk of pelvic inflammatory disease, ectopic pregnancy, and female infertility: a retrospective cohort study among primary care patients.” Clin Infect Dis 69.9 (2019): 1517–25.
  28. Hoenderboom, B., van Oeffelen, A., van Benthem, B., et al. “The Netherlands Chlamydia cohort study (NECCST) protocol to assess the risk of late complications following Chlamydia trachomatis infection in women.” BMC Infect Dis 17.1 (2017): 1–9.
  29. Morrison, R.P., Su, H., Lyng, K., Yuan, Y. “The Chlamydia trachomatis hyp operon is homologous to the groE stress response operon of Escherichia coli.” Infect Immun 58.8 (1990): 2701–5.
  30. Cerrone, M., Ma, J., Stephens, R. “Cloning and sequence of the gene for heat shock protein 60 from Chlamydia trachomatis and immunological reactivity of the protein.” Infect Immun 59.1 (1991): 79–90.
  31. Kaufmann, S.H. “Heat shock proteins and the immune response.” Immunol Today 11 (1990): 129–36.
  32. Res, P.С., Thole, J.I, de Vries, R.R. “Heat shock proteins in immunopathology.” Curr Opin Immunol 3 (1991): 924–9.
  33. Lee, K.S., Joo, B.S., Na, Y.J., et al. “Relationships between concentrations of tumor necrosis factor-α and nitric oxide in follicular fluid and oocyte quality.” J Assist Reprod Genet 17.4 (2000): 222–8.
  34. Tarín, J.J., García-Pérez, M.A., Hamatani, T., Cano, A. “Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases.” Reprod Biol Endocrinol 13.1 (2015): 1–11.
  35. Wang, S.P., Grayston, J.T. “Human serology in Chlamydia trachomatis infection with microimmunofluorescence.” J Infect Dis 130.4 (1974): 388–97.
  36. Newhall, W., Batteiger, B., Jones, R. “Analysis of the human serological response to proteins of Chlamydia trachomatis.” Infect Immun 38.3 (1982): 1181–9.
  37. Toye, B., Zhong, G., Peeling, R., Brunham, R.C. “Immunologic characterization of a cloned fragment containing the species-specific epitope from the major outer membrane protein of Chlamydia trachomatis.” Infect Immun 58.12 (1990): 3909–13.
  38. Toye, B., Laferrière, C., Claman, P., et al. “Association between antibody to the chlamydial heat-shock protein and tubal infertility.” J Infect Dis 168.5 (1993): 1236–40.
  39. Collins, J. “Male infertility: the interpretation of the diagnostic assessment.” The Year Book of Infertility (1989): 45.
  40. Kanda, Y. “Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics.” Bone Marrow Transplant 48.3 (2013): 452–8.
  41. Berestoviy, V.O., Sokol, I.V., Mahmood, A.A., et al. “A prospective study to analyze the specificity of chlamydial heat shock protein (CHSP60) antibodies to diagnose tubal infertility.” Wiadomosci Lekarskie (Warsaw) 74.2 (2021): 184–9.
  42. Tartakovsky, B., Bermas, B.L., Sthoeger, Z., et al. “Immunology: Defective maternal-fetal interaction in a murine autoimmune model.” Hum Reprod 11.11 (1996): 2408–11.

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Published

2021-12-29

How to Cite

Berestovyi, V., Mahmood, A., Martych, A., Prylutska, A., Berestovyi, O., & Govsieiev, D. (2021). Prospective study to estimate the role of different infertility factors in prediction of unsuccessful IVF outcome. REPRODUCTIVE ENDOCRINOLOGY, (62), 14–21. https://doi.org/10.18370/2309-4117.2021.62.14-21

Issue

No. 62 (2021)

Section

Treatment of infertility and pregnancy

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Copyright (c) 2021 В.О. Берестовий, А. Махмуд, А.М. Мартич, А.Б. Прилуцька, О.О. Берестовий, Д.О. Говсєєв

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