Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 10, pp 2067–2076 | Cite as

ICSI does not offer any benefit over conventional IVF across different ovarian response categories in non-male factor infertility: a European multicenter analysis

  • Panagiotis DrakopoulosEmail author
  • Juan Garcia-Velasco
  • Ernesto Bosch
  • Christophe Blockeel
  • Michel de Vos
  • Samuel Santos-Ribeiro
  • Antonis Makrigiannakis
  • Herman Tournaye
  • Nikolaos P. Polyzos
Assisted Reproduction Technologies



To evaluate whether ICSI offers any benefit compared with IVF in different ovarian response categories in case of non-male factor infertility.


This is a retrospective multicenter analysis using individual patient data, conducted in 15 tertiary referral hospitals in Europe (1 center in Belgium and 14 in Spain). The study included the first cycle of all patients undergoing ovarian stimulation for IVF or ICSI in a GnRH antagonist protocol. Only patients having either IVF or ICSI for non-male factor infertility were included. Patients were divided into 4 groups based on their ovarian response as follows: group A, poor responders (1–3 oocytes); group B, suboptimal responders (4–9 oocytes); group C, normal responders (10–15 oocytes); group D, high responders (> 15 oocytes).


In total, 4891 patients were analyzed, of whom 4227 underwent ICSI and 664 IVF. There was no significant difference for the insemination method (ICSI vs. IVF) used among the different ovarian response categories: 87% vs. 13%, 87% vs. 13%, 86% vs. 14%, 84% vs. 16%, for groups A, B, C, and D, respectively, p value = 0.35. Mean fertilization rates and embryo utilization rates were comparable between IVF and ICSI in the whole cohort. Fresh and cumulative LBR did not differ significantly for IVF and ICSI in poor, suboptimal, normal, and high responders.


There is no advantage of ICSI over IVF as insemination method for non-male factor infertility, irrespective of the ovarian response. The number of oocytes retrieved has no value for the selection of the insemination procedure in case of non-male infertility.


Fertilization rates Ovarian response Oocytes IVF ICSI 



The authors would like to thank Walter Meul and Alfredo Navarro for their contribution to the data management of the study.

Supplementary material

10815_2019_1563_MOESM1_ESM.docx (53 kb)
ESM 1 (DOCX 53 kb)


  1. 1.
    Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992;340(8810):17–8.CrossRefGoogle Scholar
  2. 2.
    De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, et al. ART in Europe, 2014: results generated from European registries by ESHRE: the European IVF-monitoring consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod. 2018;33(9):1586–601. Scholar
  3. 3.
    Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015;313(3):255–63. Scholar
  4. 4.
    Adamson GD, de Mouzon J, Chambers GM, Zegers-Hochschild F, Mansour R, Ishihara O, et al. International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2011. Fertil Steril. 2018;110(6):1067–80. Scholar
  5. 5.
    Check JH, Yuan W, Garberi-Levito MC, Swenson K, McMonagle K. Effect of method of oocyte fertilization on fertilization, pregnancy and implantation rates in women with unexplained infertility. Clin Exp Obstet Gynecol. 2011;38(3):203–5.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Luna M, Bigelow C, Duke M, Ruman J, Sandler B, Grunfeld L, et al. Should ICSI be recommended routinely in patients with four or fewer oocytes retrieved? J Assist Reprod Genet. 2011;28(10):911–5. Scholar
  7. 7.
    Tannus S, Son WY, Gilman A, Younes G, Shavit T, Dahan MH. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Hum Reprod. 2017;32(1):119–24. Scholar
  8. 8.
    Schwarze J, Jeria R, Crosby J, Villa S, Ortega O, Pommer R. Is there a reason to perform ICSI in the absence of male factor? Lessons from the Latin American Registry of ART. Human Reprod Open. 2017;2(2):1–5. Scholar
  9. 9.
    Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, et al. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016;31(2):370–6. Scholar
  10. 10.
    Polyzos NP, Drakopoulos P, Parra J, Pellicer A, Santos-Ribeiro S, Tournaye H, et al. Cumulative live birth rates according to the number of oocytes retrieved after the first ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection: a multicenter multinational analysis including approximately 15,000 women. Fertil Steril. 2018;110(4):661–70 e1. Scholar
  11. 11.
    Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–45. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Papanikolaou EG, Pozzobon C, Kolibianakis EM, Camus M, Tournaye H, Fatemi HM, et al. Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles. Fertil Steril. 2006;85(1):112–20. Scholar
  13. 13.
    Humaidan P, Polyzos NP, Alsbjerg B, Erb K, Mikkelsen AL, Elbaek HO, et al. GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients. Hum Reprod. 2013;28(9):2511–21. Scholar
  14. 14.
    Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L, et al. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26(7):1616–24. Scholar
  15. 15.
    Polyzos NP, Sunkara SK. Sub-optimal responders following controlled ovarian stimulation: an overlooked group? Hum Reprod. 2015;30(9):2005–8. Scholar
  16. 16.
    Embryology ESIGo, Alpha Scientists in Reproductive Medicine. Electronic address cbgi. The Vienna consensus: report of an expert meeting on the development of ART laboratory performance indicators. Reprod BioMed Online. 2017;35(5):494–510. Scholar
  17. 17.
    Dang VQ, Vuong LN, Ho TM, Ha AN, Nguyen QN, Truong BT, et al. The effectiveness of ICSI versus conventional IVF in couples with non-male factor infertility: study protocol for a randomised controlled trial. Hum Reprod Open. 2019;2019(2):hoz006. Scholar
  18. 18.
    Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glossary on infertility and fertility care, 2017. Hum Reprod. 2017;32(9):1786–801. Scholar
  19. 19.
    van Rumste MM, Evers JL, Farquhar CM. Intra-cytoplasmic sperm injection versus conventional techniques for oocyte insemination during in vitro fertilisation in patients with non-male subfertility. Cochrane Database Syst Rev. 2003;2:CD001301. Scholar
  20. 20.
    Rosen MP, Shen S, Dobson AT, Fujimoto VY, McCulloch CE, Cedars MI. Oocyte degeneration after intracytoplasmic sperm injection: a multivariate analysis to assess its importance as a laboratory or clinical marker. Fertil Steril. 2006;85(6):1736–43. Scholar
  21. 21.
    Li Z, Wang AY, Bowman M, Hammarberg K, Farquhar C, Johnson L, et al. ICSI does not increase the cumulative live birth rate in non-male factor infertility. Hum Reprod. 2018;33(7):1322–30. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Panagiotis Drakopoulos
    • 1
    • 2
    Email author
  • Juan Garcia-Velasco
    • 3
    • 4
  • Ernesto Bosch
    • 5
  • Christophe Blockeel
    • 1
    • 2
  • Michel de Vos
    • 1
    • 2
  • Samuel Santos-Ribeiro
    • 6
    • 7
  • Antonis Makrigiannakis
    • 8
  • Herman Tournaye
    • 1
    • 2
  • Nikolaos P. Polyzos
    • 2
    • 9
  1. 1.Center for Reproductive Medicine, Universitair Ziekenhuis BrusselVrije Universiteit BrusselBrusselsBelgium
  2. 2.Faculty of Medicine and Pharmacy, Department of Surgical and Clinical ScienceVrije Universiteit BrusselBrusselsBelgium
  3. 3.Instituto Valenciano de Infertilidad, IVI-RMA MadridMadridSpain
  4. 4.Rey Juan Carlos UniversityMadridSpain
  5. 5.Instituto Valenciano de Infertilidad, IVI-RMA ValenciaValenciaSpain
  6. 6.IVI-RMA LisbonLisbonPortugal
  7. 7.Department of Obstetrics and Gynecology, Faculty of MedicineUniversity of LisbonLisbonPortugal
  8. 8.Department of Obstetrics and Gynecology, Medical SchoolUniversity of CreteHeraklionGreece
  9. 9.Department of Reproductive MedicineDexeus University HospitalBarcelonaSpain

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