Download PDF
CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2017; 77(10): 1088-1094
DOI: 10.1055/s-0043-119543
GebFra Science
Review/Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Fertility Preservation in Female Patients with Breast Cancer – a Current Overview

Article in several languages: English | deutsch
Veronika Guenther
1   Department of Gynaecology and Obstetrics, UKSH Campus Kiel, Kiel, Germany
,
Ibrahim Alkatout
1   Department of Gynaecology and Obstetrics, UKSH Campus Kiel, Kiel, Germany
,
Wiebe Junkers
2   University Fertility Centre, Medical Care Centre, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany
,
Dirk Bauerschlag
1   Department of Gynaecology and Obstetrics, UKSH Campus Kiel, Kiel, Germany
,
Nicolai Maass
1   Department of Gynaecology and Obstetrics, UKSH Campus Kiel, Kiel, Germany
,
Soeren von Otte
2   University Fertility Centre, Medical Care Centre, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany
› Author Affiliations
Further Information

Publication History

received 02 July 2017
revised 08 September 2017

accepted 11 September 2017

Publication Date:
26 October 2017 (online)

Also available at
   Permissions and Reprints

Abstract

Many premenopausal patients who develop breast cancer have not yet completed their family planning, so measures of fertility protection to preserve their fertile potential would be beneficial. Polychemotherapy causes irreversible damage to the ovarian follicles – irrespective of whether in a neoadjuvant or adjuvant setting – and this can sometimes result in permanent infertility. Depending on which cytostatic agents are used and on the age-related ovarian reserve of the woman, gonadotoxic risk must be classified as low, moderate or high. Options of fertility preservation include: a) cryopreservation of fertilised or unfertilised oocytes. After ovarian hyperstimulation, mature oocytes are retrieved by transvaginal follicle aspiration, after which they are cryopreserved, either unfertilised or on completion of IVF or ICSI treatment. During b) cryopreservation of ovarian tissue, about 50% of the ovarian cortex of one ovary is resected with the aid of a laparoscopic procedure and cryopreserved. The application of c) GnRH agonists as a medicinal therapy option is an attempt at endocrine ovarian suppression in order to protect oocytes, granulosa cells and theca cells from the cytotoxic effect of chemotherapy.

Key words

breast cancer - fertility preservation - cryopreservation - oocytes - ovarian tissue - GnRH agonist
 

  • References/Literatur

  • 1 Allemani C, Weir HK, Carreira H. et al. CONCORD Working Group. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 2015; 385: 977-1010
    CrossrefPubMedSearch in Google Scholar
  • 2 Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V.. Atlas der Krebsinzidenz und -mortalität in Deutschland (GEKID-Atlas). 2013 Online: http://www.gekid.de last access: 04.06.2017
    PubMedSearch in Google Scholar
  • 3 Barnes B, Bertz J, Buttmann-Schweiger N. et al. Bericht zum Krebsgeschehen in Deutschland 2016. Zentrum für Krebsregisterdaten im Robert Koch Institut, November 2016. Berlin: Robert Koch-Institut; 2016; 22: 34-35
    PubMedSearch in Google Scholar
  • 4 Robert Koch-Institut. Zentrum für Krebsregisterdaten. Krebs in Deutschland. 3.14 Brustdrüse. 2012 Online: http://www.krebsdaten.de last access: 04.06.2017
    PubMedSearch in Google Scholar
  • 5 Liedtke C, Kiesel L. Chemotherapy-induced amenorrhea – an update. Geburtsh Frauenheilk 2012; 72: 809-818
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Ritzinger P, Dudenhausen JW, Holzgreve W. Risiken der späten Mutterschaft. Speculum – Zeitschrift für Gynäkologie und Geburtshilfe 2012; 30: 15-23
    PubMedSearch in Google Scholar
  • 7 Pronzato P, Mustacchi G, De Matteis A. et al. Biological characteristics and medical treatment of breast cancer in young women-a featured population: results from the NORA study. Int J Breast Cancer 2011; 2011: 534256
    PubMedSearch in Google Scholar
  • 8 Alvarez RM, Ramanathan P. Fertility preservation in female oncology patients: the influence of the type of cancer on ovarian stimulation response. Hum Reprod 2016;
    PubMedSearch in Google Scholar
  • 9 Creux H, Monnier P, Son WY. et al. Immature oocyte retrieval and in vitro oocyte maturation at different phases of the menstrual cycle in women with cancer who require urgent gonadotoxic treatment. Fertil Steril 2017; 107: 198-204
    CrossrefPubMedSearch in Google Scholar
  • 10 Ataya KM, McKanna JA, Weintraub AM. et al. A luteinizing hormone-releasing hormone agonist for the prevention of chemotherapy-induced ovarian follicular loss in rats. Cancer Res 1985; 45: 3651-3656
    PubMedSearch in Google Scholar
  • 11 Familiari G, Caggiati A, Nottola SA. et al. Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkinʼs disease. Hum Reprod 1993; 8: 2080-2087
    CrossrefPubMedSearch in Google Scholar
  • 12 Dann EJ, Epelbaum R, Avivi I. et al. Fertility and ovarian function are preserved in women treated with an intensified regimen of cyclophosphamide, adriamycin, vincristine and prednisone (Mega-CHOP) for non-Hodgkin lymphoma. Hum Reprod 2005; 20: 2247-2249
    CrossrefPubMedSearch in Google Scholar
  • 13 Walshe JM, Denduluri N, Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol 2006; 24: 5769-5779
    CrossrefPubMedSearch in Google Scholar
  • 14 Zhou W, Ding Q, Liang X. et al. The risk of amenorrhea is related to chemotherapy-induced leucopenia in breast cancer patients receiving epirubicin and taxane based chemotherapy. PLoS One 2012; 7: e37249
    CrossrefPubMedSearch in Google Scholar
  • 15 Fornier MN, Modi S, Panageas KS. et al. Incidence of chemotherapy-induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane. Cancer 2005; 104: 1575-1579
    CrossrefPubMedSearch in Google Scholar
  • 16 Martin M, Pienkowski T, Mackey J. et al. Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005; 352: 2302-2313
    CrossrefPubMedSearch in Google Scholar
  • 17 Meirow D, Nugent D. The effects of radiotherapy and chemotherapy on female reproduction. Hum Reprod Update 2001; 7: 535-543
    CrossrefPubMedSearch in Google Scholar
  • 18 Christinat A, Pagani O. Fertility after breast cancer. Maturitas 2012; 73: 191-196
    CrossrefPubMedSearch in Google Scholar
  • 19 Ruddy KJ, Partridge AH. The unique reproductive concerns of young women with breast cancer. Adv Exp Med Biol 2012; 732: 77-87
    PubMedSearch in Google Scholar
  • 20 Ruddy KJ, OʼNeill A, Miller KD. et al. Biomarker prediction of chemotherapy-related amenorrhea in premenopausal women with breast cancer participating in E5103. Breast Cancer Res Treat 2014; 144: 591-597
    CrossrefPubMedSearch in Google Scholar
  • 21 Reimer T, Kempert S, Gerber B. et al. SLCO1B1*5 polymorphism (rs4149056) is associated with chemotherapy-induced amenorrhea in premenopausal women with breast cancer: a prospective cohort study. BMC Cancer 2016; 16: 337
    CrossrefPubMedSearch in Google Scholar
  • 22 Day FR, Ruth KS, Thompson DJ. et al. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat Genet 2015; 47: 1294-1303
    CrossrefPubMedSearch in Google Scholar
  • 23 Hickey M, Peate M, Saunders CM. et al. Breast cancer in young women and its impact on reproductive function. Hum Reprod Update 2009; 15: 323-339
    CrossrefPubMedSearch in Google Scholar
  • 24 Pagani O, Ruggeri M, Manunta S. et al. Pregnancy after breast cancer: Are young patients willing to participate in clinical studies?. Breast 2015; 24: 201-207
    CrossrefPubMedSearch in Google Scholar
  • 25 International Breast Cancer Study Group. Pregnancy outcome and safety of interrupting therapy for women with endocrine responsive breast cancer (POSITIVE) – Trial. NCT 02308085. 2016 Online: https://clinicaltrials.gov/ct2/show/study/NCT02308085 last access: 08.06.2017
    PubMedSearch in Google Scholar
  • 26 Camp-Sorrell D. Cancer and its treatment effect on young breast cancer survivors. Semin Oncol Nurs 2009; 25: 251-258
    CrossrefPubMedSearch in Google Scholar
  • 27 Carter J, Chi DS, Brown CL. et al. Cancer-related infertility in survivorship. Int J Gynecol Cancer 2010; 20: 2-8
    CrossrefPubMedSearch in Google Scholar
  • 28 Penrose R, Beatty L, Mattiske J. et al. The psychosocial impact of cancer-related infertility on women: a review and comparison. Clin J Oncol Nurs 2013; 17: 188-193
    CrossrefPubMedSearch in Google Scholar
  • 29 von Wolff M. Perspektive Fertilität: Indikation und Durchführung fertilitätsprotektiver Maßnahmen bei onkologischen und nicht-onkologischen Erkrankungen. Kiel: Verlag Schmidt & Klaunig; 2016
    Search in Google Scholar
  • 30 von Wolff M, Thaler CJ, Frambach T. et al. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril 2009; 92: 1360-1365
    CrossrefPubMedSearch in Google Scholar
  • 31 Oktay K, Buyuk E, Libertella N. et al. Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol 2005; 23: 4347-4353
    CrossrefPubMedSearch in Google Scholar
  • 32 Oktay K, Hourvitz A, Sahin G. et al. Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy. J Clin Endocrinol Metab 2006; 91: 3885-3890
    CrossrefPubMedSearch in Google Scholar
  • 33 Czeromin UV. Deutsches IVF-Register (DIR). Gablitz, Österreich: Krause & Pachernegg GmbH, Verlag für Medizin und Wirtschaft; 2015: 24-25
    Search in Google Scholar
  • 34 Desai N, Blackmon H, Szeptycki J. et al. Cryoloop vitrification of human day 3 cleavage-stage embryos: post-vitrification development, pregnancy outcomes and live births. Reprod Biomed Online 2007; 14: 208-213
    CrossrefPubMedSearch in Google Scholar
  • 35 Nawroth F. Kryokonservierung. In: Nawroth F. Social Freezing. Wiesbaden: Springer Fachmedien; 2015: 88-90
    Search in Google Scholar
  • 36 Diedrich K, Ludwig M, Griesinger G. Reproduktionsmedizin. Berlin: Spinger-Verlag; 2013: 248-251
    Search in Google Scholar
  • 37 Kidder BL. In vitro maturation and in vitro fertilization of mouse oocytes and preimplantation embryo culture. Methods Mol Biol 2014; 1150: 191-199
    PubMedSearch in Google Scholar
  • 38 Benkhalifa M, Demirol A, Ménézo Y. et al. Natural cycle IVF and oocyte in-vitro maturation in polycystic ovary syndrome: a collaborative prospective study. Reprod Biomed Online 2009; 18: 29-36
    CrossrefPubMedSearch in Google Scholar
  • 39 Donnez J, Dolmans MM, Demylle D. et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 2004; 364: 1405-1410
    CrossrefPubMedSearch in Google Scholar
  • 40 Shamonki MI, Oktay K. Oocyte and ovarian tissue cryopreservation: indications, techniques, and applications. Semin Reprod Med 2005; 23: 266-276
    Thieme ConnectPubMedSearch in Google Scholar
  • 41 Macklon KT, Jensen AK, Loft A. et al. Treatment history and outcome of 24 deliveries worldwide after autotransplantation of cryopreserved ovarian tissue, including two new Danish deliveries years after autotransplantation. J Assist Reprod Genet 2014; 31: 1557-1564
    CrossrefPubMedSearch in Google Scholar
  • 42 Dittrich R, Hackl J, Lotz L. et al. Pregnancies and live births after 20 transplantations of cryopreserved ovarian tissue in a single center. Fertil Steril 2015; 103: 462-468
    CrossrefPubMedSearch in Google Scholar
  • 43 Donnez J, Dolmans MM, Pellicer A. et al. Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue: a review of 60 cases of reimplantation. Fertil Steril 2013; 99: 1503-1513
    CrossrefPubMedSearch in Google Scholar
  • 44 Dolmans MM, Luyckx V, Donnez J. et al. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue. Fertil Steril 2013; 99: 1514-1522
    CrossrefPubMedSearch in Google Scholar
  • 45 Rosendahl M, Greve T, Andersen CY. The safety of transplanting cryopreserved ovarian tissue in cancer patients: a review of the literature. J Assist Reprod Genet 2013; 30: 11-24
    CrossrefPubMedSearch in Google Scholar
  • 46 Rosendahl M, Timmermans Wielenga V, Nedergaard L. et al. Cryopreservation of ovarian tissue for fertility preservation: no evidence of malignant cell contamination in ovarian tissue from patients with breast cancer. Fertil Steril 2011; 95: 2158-2161
    CrossrefPubMedSearch in Google Scholar
  • 47 Jensen AK, Macklon KT, Fedder J. et al. 86 successful births and 9 ongoing pregnancies worldwide in women transplanted with frozen-thawed ovarian tissue: focus on birth and perinatal outcome in 40 of these children. J Assist Reprod Genet 2017; 34: 325-336
    CrossrefPubMedSearch in Google Scholar
  • 48 FertiPROTEKT N. FertiPROTEKT, Jahrestreffen Innsbruck. 2017 Online: http://www.fertiprotekt.com last access: 04.06.2017
    PubMedSearch in Google Scholar
  • 49 Pacheco F, Oktay K. Current success and efficiency of autologous ovarian transplantation: a meta-analysis. Reprod Sci 2017; 24: 1111-1120
    CrossrefPubMedSearch in Google Scholar
  • 50 Van der Ven H, Liebenthron J, Beckmann M. et al. Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates. Hum Reprod 2016; 31: 2031-2041
    CrossrefPubMedSearch in Google Scholar
  • 51 Andersen CY. Success and challenges in fertility preservation after ovarian tissue grafting. Lancet 2015; 385: 1947-1948
    CrossrefPubMedSearch in Google Scholar
  • 52 Chen H, Li J, Cui T. et al. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev 2011; (11) CD008018
    PubMedSearch in Google Scholar
  • 53 Bedaiwy MA, Abou-Setta AM, Desai N. et al. Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis. Fertil Steril 2011; 95: 906 – 14.e1-906 – 14.e4
    PubMedSearch in Google Scholar
  • 54 Moore HC, Unger JM, Phillips KA. et al. POEMS/S0230 Investigators. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 2015; 372: 923-932
    CrossrefPubMedSearch in Google Scholar
  • 55 Gerber B, Ortmann O. Muss der Ovarschutz mit GnRHa nach dem ASCO 2014 neu bewertet werden?. Frauenarzt 2015; 56: 142-145
    PubMedSearch in Google Scholar
  • 56 Lambertini M, Ceppi M, Poggio F. et al. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies. Ann Oncol 2015; 26: 2408-2419
    PubMedSearch in Google Scholar
  • 57 Lambertini M, Boni L, Michelotti A. et al. Ovarian suppression with triptorelin during adjuvant breast cancer chemotherapy and long-term ovarian function, pregnancies, and disease-free survival: a randomized clinical trial. JAMA 2015; 314: 2632-2640
    CrossrefPubMedSearch in Google Scholar
  • 58 Elgindy E, Sibai H, Abdelghani A. et al. Protecting ovaries during chemotherapy through gonad suppression: a systematic review and meta-analysis. Obstet Gynecol 2015; 126: 187-195
    CrossrefPubMedSearch in Google Scholar
  • 59 Tomasi-Cont N, Lambertini M, Hulsbosch S. et al. Strategies for fertility preservation in young early breast cancer patients. Breast 2014; 23: 503-510
    CrossrefPubMedSearch in Google Scholar