Klin Padiatr 2011; 223(3): 126-130
DOI: 10.1055/s-0031-1275292
Review

© Georg Thieme Verlag KG Stuttgart · New York

Fertility Preservation in Girls and Adolescents Before Chemotherapy and Radiation – Review of the Literature

Möglichkeiten des Fertilitätserhaltes bei Mädchen und Adoleszentinnen vor Chemo- oder Strahlentherapie – Review der LiteraturB. Lawrenz1 , M. Henes1 , E. Neunhoeffer1 , T. Fehm2 , P. Lang3 , C. P. Schwarze3
  • 1IVF-Department, Women's University Hospital Tuebingen, Germany
  • 2Women's University Hospital Tuebingen, Germany
  • 3Oncology, University Children's Hospital Tuebingen, Germany
Further Information

Publication History

Publication Date:
06 April 2011 (online)

Abstract

There has been a significant improvement in survival rates over the last decade as a result of advances in the treatment of cancer in children. One of the consequences of chemotherapy may be damage to the ovarian function, which can lead to loss of fertility. Methods of fertility protection have been developed for adult women as a result of advances in reproductive medicine, which make the option of becoming pregnant after surviving cancer realistic. However, only some of the methods can be used in prepubescent girls and adolescents. In addition, a higher number of miscarriages and premature births have been found in women who underwent pelvic radiotherapy during childhood or adolescence and the children were more commonly growth retarded. The effects of cancer treatment on the ovarian function and later fertility should be discussed at the start of treatment.

Zusammenfassung

Die Krebsbehandlung bei Kindern führt zu höhen Überlebensraten. Eine der Folgen einer Chemotherapie in der Kindheit kann eine Schädigung der Eierstocksfunktion bis zur Infertilität sein. Durch Fortschritte in der Reproduktionsmedizin sind für erwachsene Frauen fertilitätsprotektive Techniken entwickelt worden, die die Option einer Schwangerschaft nach überstandener Erkrankung realistisch erscheinen lassen. Allerdings lässt sich nur ein Teil der Maßnahmen auf präpubertäre Mädchen und Adoleszentinnen übertragen. Allerdings fanden sich bei Frauen, die in der Kindheit oder in der Adoleszenz eine Radiatio im Beckenbereich hatten, erhöhte Raten an Fehl- und Frühgeburten und die Kinder waren häufiger wachstumsretardiert. Der Einfluss der Krebstherapie auf die Eierstocksfunktion und die spätere Fruchtbarkeit sind bereits zu Therapiebeginn zu thematisieren.

References

  • 1 Anderson RA, Weddell A, Spoudeas HA. et al . Do doctors discuss fertility issues before they treat young patients with cancer?.  Hum Reprod. 2008;  23 2246-2251
  • 2 Apperley J, Carreras E, Gluckman A. et al .The EBMT Handbook. 5th Edition Haematopoietic Stem Cell Transplantation European School of Haematology 2008
  • 3 Badawy A, Elnashar A, El-Ashry M. et al . Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study.  Fertil Steril. 2009;  91 694-697
  • 4 Beck-Fruchter R, Weiss A, Shalec E. GnRH agonist therapy as ovarian protectants in female patients undergoing chemotherapy: a review of the clinical data.  Hum Reprod Update. 2008;  14 553-561
  • 5 Bedaiwy MA, El-Nashar SA, El Saman AM. et al . Reproductive outcome after transplantation of ovarian tissue: a systematic review.  Hum Reprod. 2008;  23 2709-2717
  • 6 Behringer K, Wildt L, Muller H. et al on behalf of the German Hodgkin Study Group No protection of the ovarian follicle pool with the use of GnRH-analogues or oral contraceptives in young women treated with escalated BEACOPP for advanced-stage Hodgkin lymphoma. Final results of a phase III trial from the German Hodgkin Study Group.  Ann Oncol. 2010;  Epub ahead of print
  • 7 Berry DL, Theriault RL, Holmes FA. et al . Management of breast cancer during pregnancy using a standardized protocol.  J Clin Oncol. 1999 Mar;  17 855-861
  • 8 Blumenfeld Z, von Wolff M. GnRH-analogues and oral contraceptives for fertility preservation in women during chemotherapy.  Hum Reprod Update. 2008;  14 543-552
  • 9 Byrne J, Fears TR, Gail MH. et al . Early menopause in long-term survivors of cancer during adolescence.  Am J Obstet Gynecol. 1992;  166 788-793
  • 10 Cha KY, Chung HM, Lim JM. Freezing immature oocytes.  Mol Cell Endocrinol. 2000;  169 43-47
  • 11 Chemaitilly W, Mertens AC, Mitby P. et al . Acute ovarian failure in the childhood cancer survivor study.  J Clin Endocrinol Metab. 2006;  91 1723-1728
  • 12 Chiarelli AM, Marret LD. Early menopause and infertility in females after treatment for childhood cancer diagnosed in 1964–1988 in Ontario.  Canada Am J Epidemiol. 1999;  150 245-254
  • 13 Clowse ME, Behera MA, Anders CK. et al . Ovarian Preservation by GnRH Agonists during Chemotherapy: A Meta-Analysis.  J Womens Health. 2009;  18 311-319
  • 14 Critchley HO, Wallace WH. Impact of cancer treatment on uterine function.  J Natl Cancer Inst Monogr. 2005;  34 64-68
  • 15 Dodds L, Marrett LD, Tomkins DJ. et al . Case-control study of congenital anomalies in children of cancer patients.  BMJ. 1993;  307 164-168
  • 16 Emig R, Wallwiener D, Licht P. Ovarschutz und Fertilitätserhalt vor und während der Chemotherapie.  Geburtsh Frauenheilk. 2003;  63 574-576
  • 17 Feigin E, Abir R, Fisch B. et al . Laparoscopic ovarian tissue preservation in young patients at risk for ovarian failure as a result of chemotherapy/irradiation for primary malignancy.  J Pediatr Surg. 2007;  42 862-864
  • 18 Gesundheitsberichterstattung des Bundes, . Robert-Koch-Institut: Krebs in Deutschland 2003–2004.  Häufigkeiten und Trends 2008;  6. Überarbeitete Auflage:102
  • 19 Green DM, Sklar CA, Boice JD. et al . Ovarian Failure and Reproductive Outcomes After Childhood Cancer Treatment: Results From the Childhood Cancer Survivor Study.  J Clin Oncol. 2009;  27 2374-2381
  • 20 Green DM, Whitton JA, Stovall M. et al . Pregnancy outcome of female survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.  Am J Obstet Gynecol. 2002;  187 1070-1080
  • 21 Hawkins MM. Is there evidence of a therapy-related increase in germ cell mutation among childhood cancer survivors?.  J Natl Cancer Inst. 1991;  83 1643-1650
  • 22 Hohmann C, Keil T, Reinmuth S. et al . Infertilität bei Erwachsenen nach Chemo- und Strahlentherapie im Kindes- und Jugendalter: Eine nationale Registerstudie.  Gesundheitswesen. 2010;  72 DOI: doi:10.1055/s-0030-1266690
  • 23 Holm K, Nysom K, Brocks V. Ultrasound B-mode changes in the uterus and ovaries and Doppler changes in the uterus after total body irradiation and allogeneic bone marrow transplantation in childhood.  Bone Marrow Transplantation. 1999;  23 259-263
  • 24 Jadoul P, Dolmans MM, Donnez J. Fertility preservation in girls during childhood: is it feasible, efficient and safe and to whom should it be proposed?.  Hum Reprod Update. 2010;  16 617-630
  • 25 Jemal A, Siegel R, Xu J. et al . Cancer Statistics 2009.  CA Cancer J Clin. 2010;  60 277-300
  • 26 Kim SS, Radford J, Harris M. et al . Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe for autotransplantation.  Hum Reprod. 2001;  16 2056-2060
  • 27 Körholz D, Claviez A, Hasenclever D. et al . The concept of the GPOH-HD 2003 therapy study for pediatric Hodgkin's disease: evolution in the tradition of the DAL/GPOH studies.  Klin Padiatr. 2004;  216 150-156
  • 28 Lamar C, DeCherney AH. Fertility preservation: state of the science and future research directions.  Fertil Steril. 2009;  91 316-319
  • 29 Larsen EC, Mueller J, Rechnitzer C. et al . Diminished ovarian reserve in female childhood cancer survivors with regular menstrual cycles and basal FSH <10 IU/l.  Hum Reprod. 2003;  18 417-422
  • 30 Lawrenz B, Jauckus J, Kupka M. et al . Fertility preservation in >1 000 patients – patient's characteristics, spectrum, efficacy and risks of applied preservation techniques.  Arch Gynecol Obstet. 2010;  E-pub ahead of print
  • 31 Lee SJ, Schover LR, Partridge AH. et al . American Society of Clinical Oncology recommendations on fertility preservation in cancer patients.  J Clin Oncol. 2006;  24 2917-2923
  • 32 Liu J, Malhotra R, Voltarelli J. et al . Ovarian recoverty after stem cell transplantation.  Bone Marrow Transplantation. 2008;  41 275-278
  • 33 Meirow D, Nugent D. The effects of radiotherapy and chemotherapy on female reproduction.  Hum Reprod Update. 2001;  7 535-543
  • 34 Mulvihill JJ, McKeen EA, Rosner F. et al . Pregnancy outcome in cancer patients. Experience in a large cooperative group.  Cancer. 1987;  60 1143-1150
  • 35 O’Beirne MJ, Pendola JK, Eppig JJ. A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence.  Biol Reprod. 2003;  68 1682-1686
  • 36 Oktay K, Buyuk E, Veeck L. et al . Embryo development after heterotopic transplantation of cryopreserved ovarian tissue.  Lancet. 2004;  363 837-840
  • 37 Poirot C, Brugieres L, Genestie C. et al . Ovarian tissue cryopreservation for prepubertal girls: indications and feasibility.  Gynecol Obstet Fertil. 2005;  33 799-803
  • 38 Porcu E, Bazzocchi A, Notarangelo L. et al . Human oocyte cryopreservation in infertility and oncology.  Curr Opin Endocrinol Diabetes Obes. 2008;  15 529-535
  • 39 Reinmuth S, Liebeskind AK, Wickmann L. et al . Having children after surviving cancer in childhood or adolescence – results of a Berlin survey.  Klin Padiatr. 2008;  220 159-165
  • 40 Rendtorff R, Hohmann C, Reinmuth S. et al . Hormone and Sperm Analyses after Chemo- and Radiotherapy in Childhood and Adolescence.  Klin Padiatr. 2010;  222 145-149
  • 41 Ries LA, Eisner MP, Kosary CL. et al .SEER cancer statistics review, 1973–1998.. Bethesda, MD: National Cancer Institut; 2001
  • 42 Sanders JE, Buckner CD, Amos D. et al . Ovarian function following marrow transplantation for aplastic anemia or leukemia.  J Clin Oncol. 1988;  6 813-818
  • 43 Sanders JE, Hawley J, Levy W. et al . Pregnancies following highdose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation.  Blood. 1996;  87 3045-3052
  • 44 Sankila R, Olsen JH, Anderson H. et al . Risk of cancer among offspring of childhood-cancer survivors. Association of the Nordic Cancer Registries and the Nordic Society of Paediatric Heamatology and Oncology.  N Engl J Med. 1998;  338 1339-1344
  • 45 Schellong G. The balance between cure and late effects in childhood Hodgkin's lymphoma: the experience of the German-Austrian Study-Group since 1978. German-Austrian Pediatric Hodgkin's Disease Study Group.  Ann Oncol. 1996;  7 67-72
  • 46 Schellong G, Pötter R, Brämswig J. et al . High cure rates and reduced long-term toxicity in paediatric Hodgkin's disease: the German-Austrian multicenter trial DAL-HD-90. The German-Austrian Paediatric Hodgkin's Disease Study Group.  J Clin Oncol. 1999;  17 3736-3744
  • 47 Schmidt KT, Larsen EC, Andersen CY. et al . Risk of ovarian failure and fertility preserving methods in girls and adolescents with a malignant disease.  RCOG. 2010;  117 163-174
  • 48 Signorello LB, Cohen SS, Bosetti C. et al . Female survivors of childhood cancer: Preterm birth and low birth weight among their children.  J Natl Cancer Inst. 2006;  98 1453-1461
  • 49 Sklar CA, Mertens AC, Mitby P. et al . Premature menopause in survivors of childhood cancer: A report from the childhood cancer survivor study.  J Natl Cancer Inst. 2006;  98 890-896
  • 50 Sonmezer M, Oktay K. Fertility preservation in young women undergoing breast cancer therapy.  The Oncologist. 2006;  11 422-434
  • 51 Sonmezer M, Oktay K. Fertility preservation in female patients.  Hum Reprod Update. 2004;  10 251-266
  • 52 Tao T, Del Valle A. Human oocyte and ovarian tissue cryopreservation and its application.  J Assist Reprod Genet. 2008;  25 287-296
  • 53 Von Wolff M, Kämmerer U, Kollmann Z. et al . Combination of gonadotropin-releasing hormone (GnRH) agonist with GnRH antagonists before chemotherapy reduce but does not completely prevent a follicle-stimulating hormoe flare-up.  Fertil Steril. 2011;  95 452-454
  • 54 Von Wolff M, Thaler C, Frambach T. et al . Ovarian stimulation to crypopreserve fertilized oocytes in cancer patients can be started in the luteal phase.  Fertil Steril. 2009;  92 1360-1365
  • 55 Wallace WH, Shalet SM, Hendry JH. et al . Ovarian failure following abdominal irradiation in childhood: the radiosensitivity of the human oocyte.  Br J Radiol. 1989;  62 995-998
  • 56 Wallace WH, Thomson AB, Saran F. et al . Predicting age of ovarian failure after radiation to a field that includes the ovaries.  Int J Radiat Oncol Biol Phy. 2005;  62 738-744
  • 57 Winter JF, Boice Jr JD, Frederiksen K. et al . Radiotherapy for childhood cancer and risk for congenital malformations in offspring: a population-based cohort study.  Clin Genet. 2009;  75 50-56

Correspondence

Dr. Barbara LawrenzMD 

IVF-Department

Women's University Hospital

Tuebingen

Calwerstreet 7

72076 Tuebingen

Germany

Phone: + 49/7071/29 82211

Fax: + 49/7071/29 2250

Email: barbara.lawrenz@med.uni-tuebingen.de