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Microbial contamination in assisted reproductive technology: source, prevalence, and cost

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Abstract

Even the strictest laboratories and clinics are prone to the occurrence of microbial contamination. In the case of in vitro fertilization (IVF) research and practice facilities, the number of possible sources is particularly vast. In addition to ambient air, personnel, and non-sterilized materials, follicular fluid and semen from patients are a very common gateway for a diverse range of bacteria and fungi into embryo cultures. Even so, reports of contamination cases are rare, what leads many clinics to see the issue as a negligible risk. Microbiological contamination may result in the demise of the patient’s embryos, leading to additional costs to both the patient and the clinics. Regardless of financial loss, emotional costs, and stress levels during IVF are highly distressing. Other worrisome consequences include DNA fragmentation, poor-quality embryos, early pregnancy loss or preterm birth, and possible long-term damages that need further investigation. In this review, we aimed to shed a light on the issue that we consider largely underestimated and to be the underlying cause of poor IVF outcomes in many cases. We also discuss the composition of the microbiome and how its interaction with the reproductive tract of IVF-seeking patients might influence their outcomes. In conclusion, we urge clinics to more rigorously identify, register, and report contamination occurrences, and highlight the role of the study of the microbiome to improve overall results and safety of assisted reproduction.

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References

  1. Practice Committee of American Society for Reproductive Medicine. Recommendations for reducing the risk of viral transmission during fertility treatment with the use of autologous gametes: a committee opinion. Fertil Steril. 2013;99(2):340–6.

    Google Scholar 

  2. Jindal SK, Rawlins RG, Muller CH, Drobnis EZ. Guidelines for risk reduction when handling gametes from infectious patients seeking assisted reproductive technologies. Reprod BioMed Online. 2016;33(2):121–30.

    PubMed  Google Scholar 

  3. Pelzer ES, Allan JA. The isolation and identification of microorganisms in the reproductive environment: the potential impact on the IVF culture system and on IVF outcomes. J Clin Embryol. 2012;15(3):44–53.

    Google Scholar 

  4. Foizer BRR, Silva KR, Vieira JSD, Amaral WN. Contaminação microbiológica em laboratório de reprodução humana e suas implicações no sucesso da reprodução assistida. Reproducao e Climaterio. 2014;29(2):66–70 (7).

    Google Scholar 

  5. Ben-Chetrit A, Shen O, Haran E, Brooks B, Geva-Eldar T, Margalioth EJ. Transfer of embryos from yeast-colonized dishes. Fertil Steril. 1996;66:335–7.

    CAS  PubMed  Google Scholar 

  6. Ribeiro BRF, Amaral WN, Sadoyama G. Investigação bacteriológica e micológica em placas de cultivo de embriões em laboratórios de reprodução humana. Reprod Clim. 2011;26:12–8.

    Google Scholar 

  7. Klein JU, Missmer SA, Jackson KV, Orasanu B, Fox JH, Racowsky C. In vitro fertilization outcomes after transfer of embryos contaminated with yeast. Fertil Steril. 2009;91(1):294–7.

    PubMed  Google Scholar 

  8. Kastrop PM, de Graaf-Miltenburg LA, Gutknecht DR, Weima SM. Microbial contamination of embryo cultures in an ART laboratory: sources and management. Hum Reprod. 2007;22(8):2243–8.

    PubMed  Google Scholar 

  9. Esteves SC, Benedict FC. Implementation of air quality control in reproductive laboratories in full compliance with the Brazilian cells and tissue germinative directive. Reprod BioMed Online. 2013;26:9–21.

    PubMed  Google Scholar 

  10. Pelzer ES, Allan JA, Waterhouse MA, Ross T, Beagley KW, et al. Microorganisms within human follicular fluid: effects on IVF. PLoS One. 2013;8(3):e59062.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Domes T, Lo KC, Grober ED, Mullen JB, Mazzulli T, Jarvi K. The incidence and effect of bacteriospermia and elevated seminal leukocytes on semen parameters. Fertil Steril. 2012;97(5):1050–5.

    PubMed  Google Scholar 

  12. Maduka RN, Osaikhuwuomwan JA, Aziken ME. The effect of bacterial colonization of the embryo transfer catheter on outcome of in vitro fertilization–embryo transfer treatment. Afr J Med Health Sci. 2018;17(1):7–13.

    Google Scholar 

  13. Peymani R, DeCherney A. Microbiome, infection and inflammation in infertility. In: Darwish A (Ed.). Chapter 8, InTech; 2016:99–133. https://www.intechopen.com/books/genital-infections-and-infertility/microbiome-infection-and-in- flammation-in-infertility. Accessed 29 Apr 2019.

  14. Keburia LK, Smolnikova VY, Priputnevich TV, Muravyeva VV. Uterine microbiota and its effect on reproductive outcomes. Obstet Gynecol (Moscow). 2019;2:22–7.

    Google Scholar 

  15. Moreno I, Simon C. Deciphering the effect of reproductive tract microbiota on human reproduction. Reprod Med Biol. 2019;18(1):40–50.

    PubMed  Google Scholar 

  16. Bracewell-Milnes T, Saso S, Nikolaou D, Norman-Taylor J, Johnson M, Thum MY. Investigating the effect of an abnormal cervico-vaginal and endometrial microbiome on assisted reproductive technologies: a systematic review. Am J Reprod Immunol. 2018;80(5):e13037.

    PubMed  Google Scholar 

  17. Mortimer D, Cohen J, Mortimer ST, Fawzy M, McCulloh DH. Cairo consensus on the IVF laboratory environment and air quality: report of an expert meeting. Reprod BioMed Online. 2018;36(6):658–74.

    CAS  PubMed  Google Scholar 

  18. Wenner M Humans carry more bacterial cells than human ones. Sci Am 2007;30.

  19. Virecoulon F, Wallet F, Fruchart-Flamenbaum A, Rigot JM, Peers MC, Mitchell V, et al. Bacterial flora of the low male genital tract in patients consulting for infertility. Andrologia. 2005;37(5):160–5.

    CAS  PubMed  Google Scholar 

  20. Pelzer ES, Allan JA, Cunningham K, Mengersen K, Allan JM, Launchbury T, et al. Microbial colonization of follicular fluid: alterations in cytokine expression and adverse assisted reproduction technology outcomes. Hum Reprod. 2011;26:1799–812.

    CAS  PubMed  Google Scholar 

  21. Pellati D, Mylonakis I, Bertoloni G, et al. Genital tract infections and infertility. Eur J Obstet Gynecol Reprod Biol. 2008;140(1):3–11.

    PubMed  Google Scholar 

  22. Kyono K, Hashimoto T, Kikuchi S, Nagai Y, Sakuraba Y. A pilot study and case reports on endometrial microbiota and pregnancy outcome: an analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium. Reprod Med Biol. 2018;18(1):72–82.

    PubMed  PubMed Central  Google Scholar 

  23. Peter S, Gärtner MA, Michel G, Ibrahim M, Klopfleisch R, Lübke-Becker A, et al. Influence of intrauterine administration of Lactobacillus buchneri on reproductive performance and pro-inflammatory endometrial mRNA expression of cows with subclinical endometritis. Sci Rep. 2018;8(1):5473.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Pelzer ES, Allan JA, Theodoropoulos C, Ross T, Beagley KW, Knox CL. Hormone-dependent bacterial growth, persistence and biofilm formation--a pilot study investigating human follicular fluid collected during IVF cycles. PLoS One. 2012;7(12):e49965.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Ricci S, De Giorgi S, Lazzeri E, Luddi A, Rossi S, Piomboni P, et al. Impact of asymptomatic genital tract infections on in vitro fertilization (IVF) outcome. PLoS One. 2018;13(11):e0207684.

    PubMed  PubMed Central  Google Scholar 

  26. García-Velasco JA, Menabrito M. Catalán I3. What fertility specialists should know about the vaginal microbiome: a review. Reprod BioMed Online. 2017;35(1):103–12.

    PubMed  Google Scholar 

  27. Knox CL, Allan JA, Allan JM. Ureaplasma parvum and Ureaplasma urealyticum are detected in semen after washing before assisted reproductive technology procedures. Fertil Steril. 2003;80(4):921–9.

    PubMed  Google Scholar 

  28. Palini S, Primiterra M, De Stefani S, Pedna MF, Sparacino M, Farabegoli P, et al. A new micro swim-up procedure for sperm preparation in ICSI treatments: preliminary microbiological testing. JBRA Assist Reprod. 2016;20(3):94–8.

    PubMed  PubMed Central  Google Scholar 

  29. Qing L, Song QX, Feng JL, Li HY, Liu G, Jiang HH. Prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Ureaplasma urealyticum infections using a novel isothermal simultaneous RNA amplification testing method in infertile males. Ann Clin Microbiol Antimicrob. 2017;16(1):45.

    PubMed  PubMed Central  Google Scholar 

  30. Jue JS, Ramasamy R. Significance of positive semen culture in relation to male infertility and the assisted reproductive technology process. Transl Androl Urol. 2017;6(5):916–22.

    PubMed  PubMed Central  Google Scholar 

  31. ACOG Committee on Practice Bulletins—Gynecology. ACOG practice bulletin no. 104: antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol. 2009;113(5):1180–9.

    Google Scholar 

  32. Franasiak JM, Scott RT Jr. Reproductive tract microbiome in assisted reproductive technologies. Fertil Steril. 2015;104(6):1364–71.

    PubMed  Google Scholar 

  33. Pereira N, Hutchinson AP, Lekovich JP, Hobeika E, Elias RT. Antibiotic prophylaxis for gynecologic procedures prior to and during the utilization of assisted reproductive technologies: a systematic review. J Pathog. 2016;2016:4698314.

    PubMed  PubMed Central  Google Scholar 

  34. Florio P, Fimiani R, Franchini M, Gubbini G. Is antibiotic prophylaxis necessary for hysteroscopy? In: Tinelli A, Alonso PL, Haimovich S, editors. Hysteroscopy. Springer: Cham; 2018.

    Google Scholar 

  35. Sirota I, Zarek SM, Segars JH. Potential influence of the microbiome on infertility and assisted reproductive technology. Semin Reprod Med. 2014;32:35–42.

    PubMed  PubMed Central  Google Scholar 

  36. Vicari E. Effectiveness and limits of antimicrobial treatment on seminal leukocyte concentration and related reactive oxygen species production in patients with male accessory gland infection. Hum Reprod. 2000;15:2536–44.

    CAS  PubMed  Google Scholar 

  37. Hayashi T, Miyata A, Yamada T. The impact of commonly prescribed drugs on male fertility. Hum Fertil (Camb). 2008;11(3):191–6.

    Google Scholar 

  38. Magli MC, Gianaroli L, Fiorentino A, Ferraretti AP, Fortini D, Panzella S. Improved cleavage rate of human embryos cultured in antibiotic-free medium. Hum Reprod. 1996;11(7):1520–4.

    CAS  PubMed  Google Scholar 

  39. Lancini G, Parenti F. Antibiotics an integrated view. New York: Springer; 1982. p. l–241.

    Google Scholar 

  40. Zhou H, McKiernan SH, Ji W, Bavister BD. Effect of antibiotics on development in vitro of hamster pronucleate ova. Theriogenology. 2000;54(7):999–1006.

    CAS  PubMed  Google Scholar 

  41. Swain JE. Optimal human embryo culture. Semin Reprod Med. 2015;33(2):103–17.

    PubMed  Google Scholar 

  42. Cottell E, McMorrow J, Lennon B, Fawsy M, Cafferkey M, Harrison RF. Microbial contamination in an in vitro fertilization-embryo transfer system. Fertil Steril. 1996;66(5):776–80.

    CAS  PubMed  Google Scholar 

  43. Zhu GJ, Wei YL, Hu J, Liu Q. Microorganism contamination in in vitro fertilization-embryo transfer system and their sources. Zhonghua Fu Chan Ke Za Zhi. 2004;39(6):382–4.

    PubMed  Google Scholar 

  44. Nema R, Khare S. An animal cell culture: advance technology for modern research. Adv Biosci Biotechnol. 2012;3(3):219.

    Google Scholar 

  45. Nikfarjam L, Farzaneh P. Prevention and detection of mycoplasma contamination in cell culture. Cell J (Yakhteh). 2012;13(4):203.

    Google Scholar 

  46. Pomeroy KO. Contamination of human IVF cultures by microorganisms: a review. J Clin Embryo. 2010;13:11–30.

    Google Scholar 

  47. Esteves SC, Bento FC. Implementation of cleanroom technology in reproductive laboratories: the question is not why but how. Reprod BioMed Online. 2016;32:9–11.

    PubMed  Google Scholar 

  48. Poletto KQ, Lima YAR, Approbato MS. Effect of the air filtration system replacement on embryo quality in the assisted reproduction laboratory. Rev Bras Ginecol Obstet. 2018;40:10.

    Google Scholar 

  49. Commission of the European Parliament. Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on Setting Standards of Quality and Safety for the Donation, Procurement, Testing, Processing, Preservation, Storage and Distribution of Human Tissues and Cells; 2004. http://eur-lex.europa.eu/Lex-UriServ/LexUriServ.do?uri=OJ:L:2004:102:0048:0058:en:PDF. Accessed 29 Apr 2019.

  50. ANVISA. Brazilian National Agency for Sanitary Surveillance Resolução no. 33 da Diretoria colegiada da Agência Nacional de Vigilância Sanitária (amended by RDC23 of 27 May 2011 on Setting Standards of Quality and Safety for the Donation, Procurement, Testing, Processing, Preservation, Storage and Distribution of Human Tissues and Cells); 2006. Available from http://www.bvsms.saude.gov.br/bvs/saudelegis/anvisa/2011/res0023_27_05_2011.html. Accessed 29 Apr 2019.

  51. Catt S, Lingham E, Lee W, Muthusamy Y, Kally C, et al. A randomized trial investigating the effectiveness and safety of three IVF laboratory disinfectants. Hum Reprod. 2013;28(suppl_1):i99–i101.

    Google Scholar 

  52. Pollet-Villard X, Levy R. Impact of air quality on practices and results in the IVF laboratory. Gynecol Obstet Fertil Senol. 2018;46(10–11):713–28.

    CAS  PubMed  Google Scholar 

  53. Haahr T, Jensen JS, Humaidan P. Vaginal microbiota and IVF outcomes: poor diagnosis results in flawed conclusions. Reprod BioMed Online. 2019 Jul;39(1):178.

    PubMed  Google Scholar 

  54. Volgmann T, Ohlinger R, Panzig B. Ureaplasma urealyticum-harmless commensal or underestimated enemy of human reproduction? A review Arch Gynecol Obstet. 2005;273(3):133–9.

    PubMed  Google Scholar 

  55. Burrello N, Calogero AE, Perdichizzi A, Salmeri M, D’Agata R, Vicari E. Inhibition of oocyte fertilization by assisted reproductive techniques and increased sperm DNA fragmentation in the presence of Candida albicans: a case report. Reprod BioMed Online. 2004;8:569–73.

    PubMed  Google Scholar 

  56. Shu Y, Prokai D, Berga S, Taylor R, Johnston-MacAnanny E. Transfer of IVF-contaminated blastocysts with removal of the zona pellucida resulted in live births. J Assist Reprod Genet. 2016;33(10):1385–8.

    PubMed  PubMed Central  Google Scholar 

  57. El Hajj N, Haaf T. Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction. Fertil Steril. 2013;99(3):632–41.

    PubMed  Google Scholar 

  58. Bierne H, Hamon M, Cossart P. Epigenetics and bacterial infections. Cold Spring Harb Perspect Med. 2012;2(12):a010272.

    PubMed  PubMed Central  Google Scholar 

  59. Kitamura A, Miyauchi N, Hamada H, Hiura H, Chiba H, Okae H, et al. Epigenetic alterations in sperm associated with male infertility. Congenit Anom (Kyoto). 2015;55(3):133–44.

    Google Scholar 

  60. Centers for Disease Control and Prevention. Assisted Reproductive Technology (ART); 2017. https://www.cdc.gov/art/artdata/index.html Accessed on 30 Apr 2019.

  61. Mortimer D, Mortimer ST. Quality and risk management in the IVF laboratory. 3rd ed. Cambridge, Cambridge University Press; 2005. p. 24–44.

  62. van Empel IW, Nelen WL, Hermens RP, Kremer JA. Coming soon to your clinic: high-quality ART. Hum Reprod. 2008;23:1242–5.

    PubMed  Google Scholar 

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Correspondence to E. D. Borges.

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Borges, E.D., Berteli, T.S., Reis, T.F. et al. Microbial contamination in assisted reproductive technology: source, prevalence, and cost. J Assist Reprod Genet 37, 53–61 (2020). https://doi.org/10.1007/s10815-019-01640-5

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