Fertilitätserhalt bei Patienten in der Dermatoonkologie – Eine aktuelle Übersicht

Zusammenfassung

Bei vielen Patienten, die an einem Malignom 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, Molekular- oder Immuntherapien kann es zu einer irreversiblen Schädigung der Follikel bzw. Spermatogenese kommen, was u. U. zu einer permanenten Infertilität führen kann. Abhängig von der verwendeten Therapie und der altersabhängigen Ovarialreserve der Frau muss das gonadotoxische Risiko als niedrig, mittel oder hoch eingeschätzt werden. Möglichkeiten des Fertilitäserhalts 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 jeweiligen Therapie zu schützen. Bei männlichen Patienten können Spermien vor Therapiebeginn kryokonserviert werden.

Abstract

In many patients suffering from malignant tumours, family planning is not yet complete, so that fertility protection measures are useful for maintaining fertile potential. Polychemotherapy, whether in the neoadjuvant or adjuvant setting, molecular or immune therapies, can cause irreversible damage to the follicles or spermatogenesis, which may lead to permanent infertility. Depending on the therapy used and the age-related ovarian reserve of the woman, the gonadotoxic risk must be assessed as low, medium or high. Possible ways of preserving fertility are: a) the cryopreservation of fertilised or unfertilised oocytes. After ovarian hyperstimulation, mature oocytes are obtained by transvaginal follicle aspiration and then either unfertilized or cryopreserved after IVF or ICSI treatment. In b) cryopreservation of ovarian tissue, about 50 % of the ovarian cortex of an ovary is resected and cryopreserved by means of a laparoscopic procedure. The use of c) GnRH agonists as a drug therapy option is an attempt at endocrine ovarian suppression to protect oocytes, granulosa and theca cells from the cytotoxic influence of the respective therapy. In male patients, sperm can be cryopreserved before the start of therapy.

Publikationsverlauf

Artikel online veröffentlicht:
22. April 2021

• Literatur

• 1 Allemani C, Weir HK, Carreira H. et al. 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 Robert-Koch-Institut, Zentrum für Krebsregisterdaten. Im Internet: https://www.krebsdaten.de/Krebs/DE/Content/Krebsarten/Melanom/melanom_inhalt.html
• 3 Ritzinger P, Dudenhausen JW, Holzgreve W. Risiken der späten Mutterschaft. Speculum, Zeitschrift für Gynäkologie und Geburtshilfe 2012; 30: 15-23
• 4 Alvarez RM, Ramanathan P. Fertility preservation in female oncology patients: the influence of the type of cancer on ovarian stimulation response. Hum Reprod 2018; 33: 2051-2059
• 5 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
• 6 Walter JR, Xu S, Paller AS. et al. Oncofertility considerations in adolescents and young adults given a diagnosis of melanoma: Fertility risk of Food and Drug Administration-approved systemic therapies. J Am Acad Dermatol 2016; 75: 528-534
• 7 Ataya KM, McKanna JA, Weitraub 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
• 8 Familiari G, Caggiati A, Nottola SA. et al. Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkin's disease. Hum Reprod 1993; 8: 2080-2087
• 9 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
• 10 Albarel F, Gaudy C, Castinetti F. et al. Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma. Eur J Endocrinol 2015; 172: 195-204
• 11 Faje AT, Sullivan R, Lawrence D. et al. Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma. J Clin Endocrinol Metab 2014; 99: 4078-4085
• 12 Administration, F.a.D. List of pregnancy exposure registries. Im Internet (1.2.2016): http://www.fda.gov/ScienceResearch/SpecialTopics/WomensHealthResearch/ucm134848.htm
• 13 Ruddy KJ, Partridge AH. The unique reproductive concerns of young women with breast cancer. Adv Exp Med Biol 2012; 732: 77-87
• 14 Meirow D. Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol 2000; 169: 123-131
• 15 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
• 16 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
• 17 Day FR, Ruth KD, 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
• 18 Camp-Sorrell D. Cancer and its treatment effect on young breast cancer survivors. Semin Oncol Nurs 2009; 25: 251-258
• 19 Carter J, Chi DS, Brown CL. et al. Cancer-related infertility in survivorship. Int J Gynecol Cancer 2010; 20: 2-8
• 20 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
• 21 von Wolff M. Perspektive Fertilität: Indikation und Durchführung fertilitätsprotektiver Maßnahmen bei onkologischen und nicht-onkologischen Erkrankungen. Kiel: Schmidt & Klaunig; 2016
• 22 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
• 23 Ute Czeromin UV. Deutsches IVF-Register (DIR). 2015
• 24 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
• 25 Diedrich K, Ludwig M, Griesinger G. Reproduktionsmedizin. Berlin: Spinger; 2013: 248-251
• 26 Donnez J, Dolmans MM, Demylle D. et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet 2004; 364: 1405-1410
• 27 Shamonki MI, Oktay K. Oocyte and ovarian tissue cryopreservation: indications, techniques, and applications. Semin Reprod Med 2005; 23: 266-276
• 28 Macklon KT, Klüver Jensen A, 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
• 29 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
• 30 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
• 31 FertiPROTEKT. Jahrestreffen Innsbruck. www.fertiprotekt.com 2017
• 32 Pacheco F, Oktay K. Current Success and Efficiency of Autologous Ovarian Transplantation: A Meta-Analysis. Reprod Sci 2017; 24: 1111-1120
• 33 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
• 34 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
• 35 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.e1-4
• 36 Moore HCF, Unger JM, Phillips K-A. et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N Engl J Med 2015; 372: 923-932
• 37 Gerber B, Ortmann O. Muss der Ovarschutz mit GnRHa nach dem ASCO 2014 neu bewertet werden?. Frauenarzt 2015; 56: 142-144
• 38 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
• 39 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
• 40 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
• 41 Liedtke C, Kiesel L. Chemotherapy-Induced Amenorrhea – An Update. Geburtshilfe Frauenheilkd 2012; 72: 809-818
• 42 Tomasi-Cont N, Lambertini M, Hulsbosch S. et al. Strategies for fertility preservation in young early breast cancer patients. Breast 2014; 23: 503-510