RSS-Feed abonnieren
![](/products/assets/desktop/img/oa-logo.png)
DOI: 10.1055/s-0043-119543
Fertilitätserhalt bei Patientinnen mit Mammakarzinom – eine aktuelle Übersicht
Artikel in mehreren Sprachen: English | deutschPublikationsverlauf
received 02. Juli 2017
revised 08. September 2017
accepted 11. September 2017
Publikationsdatum:
26. Oktober 2017 (online)
![](https://www.thieme-connect.de/media/gebfra/201710/lookinside/thumbnails/10-1055-s-0043-119543_gf4575451_de-1.jpg)
Zusammenfassung
Bei vielen prämenopausalen Patientinnen, die an einem Mammakarzinom erkranken, ist die Familienplanung noch nicht abgeschlossen, sodass für den Erhalt des fertilen Potenzials Maßnahmen der Fertilitätsprotektion sinnvoll sind. Durch eine Polychemotherapie – unabhängig ob im neoadjuvanten oder adjuvanten Setting – kommt es zu einer irreversiblen Schädigung der Follikel, was unter Umständen zu einer permanenten Infertilität führen kann. Abhängig von den verwendeten Zytostatika und der altersabhängigen Ovarialreserve der Frau, muss das gonadotoxische Risiko als niedrig, mittel oder hoch eingeschätzt werden. Möglichkeiten des Fertilitätserhalts sind: a) die Kryokonservierung von fertilisierten oder unfertilisierten Oozyten. Hierbei werden nach ovarieller Hyperstimulation reife Oozyten mittels transvaginaler Follikelaspiration gewonnen und im Anschluss entweder unfertilisiert oder nach erfolgter IVF- oder ICSI-Behandlung kryokonserviert. Bei b) der Kryokonservierung von Ovarialgewebe wird mithilfe eines laparoskopischen Eingriffs etwa 50% des Ovarkortex eines Ovars reseziert und kryokonserviert. Die Verwendung von c) GnRH-Agonisten als medikamentöse Therapieoption unternimmt den Versuch einer endokrinen Ovarialsuppression, um Oozyten, Granulosa- und Thekazellen vor dem zytotoxischen Einfluss der Chemotherapie zu schützen.
-
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
- 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
- 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
- 4 Robert Koch-Institut. Zentrum für Krebsregisterdaten. Krebs in Deutschland. 3.14 Brustdrüse. 2012 Online: http://www.krebsdaten.de last access: 04.06.2017
- 5 Liedtke C, Kiesel L. Chemotherapy-induced amenorrhea – an update. Geburtsh Frauenheilk 2012; 72: 809-818
- 6 Ritzinger P, Dudenhausen JW, Holzgreve W. Risiken der späten Mutterschaft. Speculum – Zeitschrift für Gynäkologie und Geburtshilfe 2012; 30: 15-23
- 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
- 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; DOI: 10.1093/humrep/dew158.
- 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
- 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
- 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
- 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
- 13 Walshe JM, Denduluri N, Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol 2006; 24: 5769-5779
- 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
- 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
- 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
- 17 Meirow D, Nugent D. The effects of radiotherapy and chemotherapy on female reproduction. Hum Reprod Update 2001; 7: 535-543
- 18 Christinat A, Pagani O. Fertility after breast cancer. Maturitas 2012; 73: 191-196
- 19 Ruddy KJ, Partridge AH. The unique reproductive concerns of young women with breast cancer. Adv Exp Med Biol 2012; 732: 77-87
- 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
- 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
- 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
- 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
- 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
- 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
- 26 Camp-Sorrell D. Cancer and its treatment effect on young breast cancer survivors. Semin Oncol Nurs 2009; 25: 251-258
- 27 Carter J, Chi DS, Brown CL. et al. Cancer-related infertility in survivorship. Int J Gynecol Cancer 2010; 20: 2-8
- 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
- 29 von Wolff M. Perspektive Fertilität: Indikation und Durchführung fertilitätsprotektiver Maßnahmen bei onkologischen und nicht-onkologischen Erkrankungen. Kiel: Verlag Schmidt & Klaunig; 2016
- 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
- 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
- 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
- 33 Czeromin UV. Deutsches IVF-Register (DIR). Gablitz, Österreich: Krause & Pachernegg GmbH, Verlag für Medizin und Wirtschaft; 2015: 24-25
- 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
- 35 Nawroth F. Kryokonservierung. In: Nawroth F. Social Freezing. Wiesbaden: Springer Fachmedien; 2015: 88-90
- 36 Diedrich K, Ludwig M, Griesinger G. Reproduktionsmedizin. Berlin: Spinger-Verlag; 2013: 248-251
- 37 Kidder BL. In vitro maturation and in vitro fertilization of mouse oocytes and preimplantation embryo culture. Methods Mol Biol 2014; 1150: 191-199
- 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
- 39 Donnez J, Dolmans MM, Demylle D. et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 2004; 364: 1405-1410
- 40 Shamonki MI, Oktay K. Oocyte and ovarian tissue cryopreservation: indications, techniques, and applications. Semin Reprod Med 2005; 23: 266-276
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 48 FertiPROTEKT N. FertiPROTEKT, Jahrestreffen Innsbruck. 2017 Online: http://www.fertiprotekt.com last access: 04.06.2017
- 49 Pacheco F, Oktay K. Current success and efficiency of autologous ovarian transplantation: a meta-analysis. Reprod Sci 2017; 24: 1111-1120
- 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
- 51 Andersen CY. Success and challenges in fertility preservation after ovarian tissue grafting. Lancet 2015; 385: 1947-1948
- 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
- 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
- 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
- 55 Gerber B, Ortmann O. Muss der Ovarschutz mit GnRHa nach dem ASCO 2014 neu bewertet werden?. Frauenarzt 2015; 56: 142-145
- 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
- 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
- 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
- 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