Determinants of utilization of cryopreservation of germ cells in adolescent cancer patients in four European countries

  • Magdalena Balcerek
  • Ralph Schilling
  • Julianne Byrne
  • Uta Dirksen
  • Holger Cario
  • Marta Julia Fernandez-Gonzalez
  • Tomas Kepak
  • Elisabeth Korte
  • Jarmila Kruseova
  • Marina Kunstreich
  • Herwig Lackner
  • Thorsten Langer
  • Malgorzata Sawicka-Zukowska
  • Joanna Stefanowicz
  • Gabriele Strauß
  • Anja Borgmann-StaudtEmail author
  • PanCareLIFE
Original Article


Infertility is a relevant late-effect following cancer treatment; yet, a large proportion of survivors cannot recall having been informed of this risk. In an intervention study, we examined if and how supportive patient information material on fertility/fertility-preserving measures influences utilization of cryopreservation in adolescent cancer patients. The control group, recruited 03/2014–01/2016, received the usual patient education at initial diagnosis. The intervention group, recruited 04/2016–10/2017, received patient education supported by a fertility flyer and brochure. Patients and parents were each asked questions on utilization of cryopreservation in a questionnaire 3 and 6 months after initial diagnosis. Patient core and therapy data were obtained from medical records. Overall, cryopreservation rates showed no significant difference between the control (32.7%, n = 37/113) and intervention group (36.6%, n = 37/101). In the control group, cryopreservation was associated with gender (OR 0.100, CI 0.023–0.427), age (OR 1.559, CI 1.077–2.258) and recalling information on fertility protection (OR 33.663, CI 2.100–539.574); in the intervention group, cryopreservation was related to gender (OR 0.093, CI 0.026–0.330) and the estimated infertility risk (OR 43.665, CI 2.157–883.974).

Conclusion: Cryopreservation rates did not overall increase following the intervention; however, the individual risk seemed to be brought into attention more: Those at risk, including younger patients, cryopreserved at higher rates.

What is Known:

•Infertility is a relevant late-effect following adolescent cancer.

•Guidelines recommend to offer fertility protection before cancer treatment.

•A relevant proportion of adolescents with cancer are not aware of this risk.

•Fertility protection seems under-used in cancer patients at risk for infertility.

What is New:

•Information material on fertility and protection in adolescents did not increase overall rates of cryopreservation.

•Cryopreservation rates were improved according to individual risk for infertility.

•Our flyers and brochures on fertility in cancer patients are available in various languages.


Patient education Childhood and adolescent cancer Fertility impairment Fertility protection Cryopreservation Patient empowerment 


Authors’ contributions

MB: study concept and design, data acquisition, data interpretation, manuscript preparation, editing, revision and proof. RS: study concept and design, data acquisition, quality control of data and algorhythms; data analysis and interpretation; statistical analysis, manuscript editing, revisiona and proof. JB: study concept and design, manuscript editing. UD: data acquisition, manuscript editing. HC: data acquisition, manuscript editing. MJFG: manuscript editing. TK: data acquisition, manuscript editing. EK: study concept and design, data acquisition, quality control of data and algorhythms, manuscript editing. JK: data acquisition, manuscript editing. MK: data acquisition, manuscript editing. HL: data acquisition, manuscript editing. TL: data acquisition, manuscript editing. MSZ: data acquisition, manuscript editing. JS: data acquisition, manuscript editing. GS: data acquisition, manuscript editing. AB: study concept and design, data acquisition, data interpretation, manuscript editing.

Funding information

This project received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030 (PanCareLIFE). The study was also supported by Berliner Krebsgesellschaft e.V. (EKPS201607) and KINDERHILFE - Hilfe für krebs- und schwerkranke Kinder e.V. Dr. Balcerek is being supported by the Clinician Scientist Programme of Charité–Universitätsmedizin Berlin and the Berlin Institute of Health (BIH). Special thanks go to our young patients and their parents for participating in this study. We also thank the participating clinics in this study for the good cooperation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The coordinating study centre Charité-Universitätsmedizin Berlin received approval from their local ethics committee on 04/04/2014 (EA2/155/11). All data providers received approval for the study from their respective ethics committees.

Informed consent

Informed consent was obtained from all participants included in the study.


  1. 1.
    Hohmann C, Borgmann-Staudt A, Rendtorff R, Reinmuth S, Holzhausen S, Willich SN et al (2011) Patient counselling on the risk of infertility and its impact on childhood cancer survivors: results from a national survey. J Psychosoc Oncol 29:274–285CrossRefGoogle Scholar
  2. 2.
    Zebrack BJ, Casillas J, Nohr L, Adams H, Zeltzer LK (2004) Fertility issues for young adult survivors of childhood cancer. Psychooncology. 13:689–699CrossRefGoogle Scholar
  3. 3.
    Klosky JL, Anderson LE, Russell KM, Huang L, Zhang H, Schover LR et al (2017) Provider influences on sperm banking outcomes among adolescent males newly diagnosed with cancer. J Adolesc Health 60:277–283CrossRefGoogle Scholar
  4. 4.
    Korte E, Schilling R, Balcerek M, Campbell H, Dirksen U, Herrmann G, Kepak T, Kruseova J, Kunstreich M, Lackner H, Langer T, Panasiuk A, Stefanowicz J, Strauß G, Ranft A, Byrne J, Goldbeck L, Borgmann-Staudt A (2019) Fertility education for adolescent cancer patients: gaps in current clinical practice in Europe [under review 30.08.2019] .Google Scholar
  5. 5.
    Dittrich R, Kliesch S, Schuring A, Balcerek M, Baston-Bust DM, Beck R et al (2018) Fertility Preservation for patients with malignant disease. Guideline of the DGGG, DGU and DGRM (S2k-Level, AWMF Registry No. 015/082, November 2017) - Recommendations and Statements for Girls and Women. Geburtshilfe Frauenheilkd 78:567–584CrossRefGoogle Scholar
  6. 6.
    Sanger N, Jarisch A, Ochsendorf F, Klingebiel T, Liebenthron J, Kliesch S et al (2018) Fertility preservation in prepubertal und pubertal children and adolescents. Klin Padiatr.
  7. 7.
    Rashedi AS, de Roo SF, Ataman LM, Edmonds ME, Silva AA, Scarella A et al (2018) Survey of fertility preservation options available to patients with cancer around the globe. JGO 4:1–16. CrossRefGoogle Scholar
  8. 8.
    Europe EWGoOCi, Shenfield F, de Mouzon J, Scaravelli G, Kupka M, Ferraretti AP et al (2017) Oocyte and ovarian tissue cryopreservation in European countries: statutory background, practice, storage and use. HROpen 2017:hox003Google Scholar
  9. 9.
    Skinner R, Mulder RL, Kremer LC, Hudson MM, Constine LS, Bardi E et al (2017) Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium. Lancet Oncol 18:e75–e90CrossRefGoogle Scholar
  10. 10.
    Romao RL, Lorenzo AJ (2017) Fertility preservation options for children and adolescents with cancer. Can Urol Assoc J 11:S97–S102CrossRefGoogle Scholar
  11. 11.
    Ferrari S, Paffoni A, Filippi F, Busnelli A, Vegetti W, Somigliana E (2016) Sperm cryopreservation and reproductive outcome in male cancer patients: a systematic review. Reprod BioMed Online 33:29–38CrossRefGoogle Scholar
  12. 12.
    Daudin M, Rives N, Walschaerts M, Drouineaud V, Szerman E, Koscinski I et al (2015) Sperm cryopreservation in adolescents and young adults with cancer: results of the French national sperm banking network (CECOS). Fertil Steril 103:478–86 e1CrossRefGoogle Scholar
  13. 13.
    Klosky JL, Lehmann V, Flynn JS, Su Y, Zhang H, Russell KM et al (2018) Patient factors associated with sperm cryopreservation among at-risk adolescents newly diagnosed with cancer. Cancer. 124:3567–3575CrossRefGoogle Scholar
  14. 14.
    Fathi R, Rezazadeh Valojerdi M, Ebrahimi B, Eivazkhani F, Akbarpour M, Tahaei LS et al (2017) Fertility preservation in cancer patients: in vivo and in vitro options. Cell J 19:173–183Google Scholar
  15. 15.
    Lobo RA (2005) Potential options for preservation of fertility in women. N Engl J Med 353:64–73CrossRefGoogle Scholar
  16. 16.
    Donnez J, Dolmans MM (2017) Fertility preservation in women. N Engl J Med 377(17):1657–1665CrossRefGoogle Scholar
  17. 17.
    Kamiyama R, Funata N (1976) A study of leukemic cell infiltration in the testis and ovary. Bull Tokyo Med Dent Univ 23:203–210Google Scholar
  18. 18.
    Reid H, Marsden HB (1980) Gonadal infiltration in children with leukaemia and lymphoma. J Clin Pathol 33:722–729CrossRefGoogle Scholar
  19. 19.
    Somjee S, Kurkure PA, Chinoy RF, Deshpande RK, Advani SH (1999) Metastatic ovarian neuroblastoma: a case report. Pediatr Hematol Oncol 16:459–462CrossRefGoogle Scholar
  20. 20.
    Byrne J, Grabow D, Campbell H, O'Brien K, Bielack S, Am Zehnhoff-Dinnesen A et al (2018) PanCareLIFE: the scientific basis for a European project to improve long-term care regarding fertility, ototoxicity and health-related quality of life after cancer occurring among children and adolescents. Eur J Cancer 103:227–237CrossRefGoogle Scholar
  21. 21.
    Cohen J (1988) Statistical power analysis for the behavioural sciences. Lawrence Erlbaum Associates, HillsdaleGoogle Scholar
  22. 22.
    Faul F, Erdfelder E, Buchner A, Lang AG (2009) Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 41:1149–1160CrossRefGoogle Scholar
  23. 23.
    OECD. Classifying educational programmes manual for ISCED-97 implementation in OECD countries 1999 Edition.
  24. 24.
    Vesali S, Navid B, Mohammadi M, Karimi E, Omani-Samani R (2019) Little information about fertility preservation is provided for cancer patients: a survey of oncologists’ knowledge, attitude and current practice. Eur J Cancer Care (Engl) 28:e12947CrossRefGoogle Scholar
  25. 25.
    Quinn GP, Vadaparampil ST, Gwede CK, Miree C, King LM, Clayton HB et al (2007) Discussion of fertility preservation with newly diagnosed patients: oncologists' views. J Cancer Surviv 1:146–155CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Magdalena Balcerek
    • 1
    • 2
  • Ralph Schilling
    • 1
  • Julianne Byrne
    • 3
  • Uta Dirksen
    • 4
    • 5
  • Holger Cario
    • 6
  • Marta Julia Fernandez-Gonzalez
    • 1
  • Tomas Kepak
    • 7
  • Elisabeth Korte
    • 1
  • Jarmila Kruseova
    • 8
  • Marina Kunstreich
    • 9
  • Herwig Lackner
    • 10
  • Thorsten Langer
    • 11
  • Malgorzata Sawicka-Zukowska
    • 12
  • Joanna Stefanowicz
    • 13
  • Gabriele Strauß
    • 14
  • Anja Borgmann-Staudt
    • 1
    Email author
  • PanCareLIFE
  1. 1.Charité – UniversitätsmedizinBerlinGermany
  2. 2.Berlin Institute of Health (BIH)BerlinGermany
  3. 3.Boyne Research InstituteDroghedaIreland
  4. 4.West German Cancer CentreUniversity Hospital Essen Paediatrics IIIEssenGermany
  5. 5.German Cancer Research Centre (DKTK)HeidelbergGermany
  6. 6.Department of Paediatrics and Adolescent MedicineUniversity Medical CentreUlmGermany
  7. 7.University HospitalBrnoCzech Republic
  8. 8.Motol Teaching HospitalPragueCzech Republic
  9. 9.Department of Paediatric Oncology, Haematology and Immunology, Medical Faculty, Heinrich-HeineUniversity ofDüsseldorfGermany
  10. 10.Medical University ofGrazAustria
  11. 11.Lübeck UniversitätklinikLübeckGermany
  12. 12.Uniwersytet wBialymstokuPoland
  13. 13.Klinika PediatriiHematologii I Onkologii Gdanski UniwersytetGdanskPoland
  14. 14.Helios Kliniken Berlin-Buch, Klinik für Kinder- und JungendmedizinBerlinGermany

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