Geburtshilfe Frauenheilkd 2007; 67(6): 620-627
DOI: 10.1055/s-2007-965310
Übersicht

Georg Thieme Verlag KG Stuttgart · New York

Fertilitätserhaltung und Ovarprotektion bei Tumorerkrankungen: Bereits ein Standard?

Preservation of Fertility and Ovarian Protection in Tumor Patients: Is there a Standard?B. Gerber1 , H. Müller2 , T. Reimer1
  • 1Universitäts-Frauenklinik Rostock (Mitglied im Netzwerk FertiProtekt [www.fertiprotekt.de])
  • 2Praxiszentrum Frauenheilkunde am Klinikum Südstadt Rostock (Mitglied im Netzwerk FertiProtekt [www.fertiprotekt.de])
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Publikationsverlauf

eingereicht 30.1.2007

akzeptiert 23.4.2007

Publikationsdatum:
04. Juli 2007 (online)

Zusammenfassung

Die Therapie gynäkologischer und nicht gynäkologischer Tumoren bei prämenopausalen Patientinnen steht in unmittelbarem Zusammenhang mit der Erhaltung der Fertilität bzw. der ovariellen Hormonproduktion. So werden beim prämenopausalen Mammakarzinom derzeit die Ovarprotektion mit GnRH-Agonisten, Kryokonservierung von Ovarialgewebe, Eizellen oder Embryonen diskutiert. Beim Mammakarzinom gibt es derzeit keine evidenzbasierte Empfehlung für die Erhaltung der Fertilität oder Ovarialfunktion. Mit Ausnahme der Kryokonservierung von befruchteten Eizellen sind alle anderen Verfahren experimentell. Insbesondere ist die wiedereinsetzende Hormonproduktion und deren möglicher negativer Einfluss auf okkulte hormonrezeptorpositive Tumorzellen noch unklar. Patientinnen mit einer chemotherapieinduzierten Amenorrhö scheinen gegenüber weiter menstruierenden Frauen einen Vorteil im Überleben zu haben. Bei gut differenzierten Frühstadien des Endometriumkarzinoms (G1) und fehlender Myometriuminfiltration ist eine zeitlich begrenzte Remission unter Gestagen, mit nachfolgender Schwangerschaft, möglich. Die radikale vaginale Trachelektomie beim frühen Zervixkarzinom (FIGO Ia - b1) stellt eine Option zur Fertilitätserhaltung dar, wobei als wesentlicher Nachteil Zervixstenosen und die hohe Rate an Frühgeburten zu nennen ist. In Abhängigkeit vom FIGO-Tumorstadium, Grading, Ploidie-Status, histologischem Subtyp und dem Wunsch der Patientin ist bei Borderline-Tumoren, FIGO Ia(-c)-Ovarialkarzinomen und malignen Keimzelltumoren ein organerhaltendes Vorgehen mit einfacher Tumorektomie, ein- oder beidseitiger Ovarteilresektion oder unilateraler Adnexexstirpation möglich. Die Rezidivrate nach organerhaltender Operation eines Borderline- oder FIGO Ia low-grade Tumors sind mit 10 % gegenüber radikaler OP erhöht, während das Gesamtüberleben vergleichbar ist. Bei nicht gynäkologischen Tumoren geht es um den Schutz der Ovarien vor Radiatio und Chemotherapie. Hierzu können alle genannten Verfahren Anwendung finden, wobei die wiedereinsetzende Hormonproduktion keine Bedeutung hat.

Abstract

The treatment of most gynecological and non-gynecological tumors and breast cancer in premenopausal patients may influence fertility and ovarian function. In patients with breast cancer who wish to avoid a chemotherapy-induced amenorrhea (CIA) and to preserve their fertility, ovarian protection by GnRH agonists, cryoconservation of operatively sampled ovarian tissue, fertilized or unfertilized eggs, or embryos obtained by in vitro fertilization are all potential options. But there is no evidence-based recommendation for the preservation of fertility or ovarian function in breast cancer patients. Except for cryoconservation of embryos all other procedures are under investigation. The reappearance of premenopausal ovarian hormone levels may influence occult hormone-sensitive tumor cells. In patients with early stage and well differentiated endometrial cancer (G1) and no myometrium invasion a complete remission is possible by progestagens. Because of the high recurrence rate the patient must get pregnant immediately after remission. Radical vaginal trachelectomy is suitable to preserve the uterus in early cervical cancer (FIGO Ia - b1) patients. However, the rates of cervical stenosis and very early preterm deliveries are not negligible. Depending on the FIGO-stage, grade, ploidy status, histological subtype in compliant patients with borderline tumors, FIGO Ia(-c) stage ovarian cancer and malignant germ cell tumors, fertility preservation surgery consisting of unilateral adnexectomy, uni- or bilateral partial ovary resection or tumorectomy is possible. Recurrence rates after fertility preserving surgery of borderline or FIGO Ia low-grade tumors amounted to 10 % over that after radical surgery, however the overall survival rates are comparable. In cases of non-gynecological cancer ovarian protection and fertility preservation in advance of radio- or chemotherapy is unlimitedly possible, because the reappearance of ovarian hormones is harmless.

Literatur

  • 1 Donnez J, Dolmans M M, Demylle D. et al . Livebirth after orthotopic transplantation of cryopreserved ovarian tissue.  Lancet. 2004;  364 1405-1410
  • 2 Lee S J, Schover L R, Partridge A H. et al . American Society of Clinical Oncology recommendations on fertility preservation in cancer patients.  J Clin Oncol. 2006;  24 2917-2931
  • 3 Pritchard K I. Adjuvant therapy for premenopausal women with breast cancer: is it time for another paradigm shift?.  J Clin Oncol. 2002;  20 4611-4614
  • 4 Fornier M N, Modi S, Panageas K S. 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
  • 5 Ganz P A, Greendale G A, Petersen L. et al . Breast cancer in younger women: reproductive and late health effects of treatment.  J Clin Oncol. 2003;  21 4184-4193
  • 6 Nystedt M, Berglund G, Bolund C. et al . Side effects of adjuvant endocrine treatment in premenopausal breast cancer patients: a prospective randomized study.  J Clin Oncol. 2003;  21 1836-1844
  • 7 Tchen N, Juffs H G, Downie F P. et al . Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer.  J Clin Oncol. 2003;  21 4175-4183
  • 8 De Haes H, Olschewski M, Kaufmann M. et al . Quality of life in goserelin-treated versus cyclophosphamide + methotrexate + fluorouracil-treated premenopausal and perimenopausal patients with node-positive, early breast cancer: the Zoladex Early Breast Cancer Research Association Trialists Group.  J Clin Oncol. 2003;  21 4510-4516
  • 9 Ghidoni R, Boccardi M, Benussi L. et al . Effects of estrogens on cognition and brain morphology: involvement of the cerebellum.  Maturitas. 2006;  54 222-228
  • 10 EBCTCG . Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.  Lancet. 2005;  365 1687-1717
  • 11 Duffy C M, Allen S M, Clark M A. Discussions regarding reproductive health for young women with breast cancer undergoing chemotherapy.  J Clin Oncol. 2005;  23 766-773
  • 12 Holmberg L, Anderson H. HABITS (hormonal replacement therapy after breast cancer - is it safe?), a randomised comparison: trial stopped.  Lancet. 2004;  363 453-455
  • 13 Ataya K M, Palmer K C, Blacker C M. et al . Inhibition of rat ovarian [3H]thymidine uptake by luteinizing hormone-releasing hormone agonists: a possible mechanism for preventing damage by cytotoxic agents.  Cancer Res. 1988;  48 7252-7256
  • 14 Muller H. Effects of adjuvant chemotherapy of breast cancer on gonadal function.  Zentralbl Gynakol. 1990;  112 795-801
  • 15 Sklar C A, Mertens A C, 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
  • 16 Chemaitilly W, Mertens A C, Mitby P. et al . Acute ovarian failure in the childhood cancer survivor study.  J Clin Endocrinol Metab. 2006;  91 1723-1728
  • 17 Petrek J A, Naughton M J, Case L D. et al . Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study.  J Clin Oncol. 2006;  24 1045-1051
  • 18 Kauff N D, Satagopan J M, Robson M E. et al . Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation.  N Engl J Med. 2002;  346 1609-1615
  • 19 Rebbeck T R, Lynch H T, Neuhausen S L. et al . Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.  N Engl J Med. 2002;  346 1616-1622
  • 20 EBCTCG . Ovarian ablation for early breast cancer.  Cochrane Database Syst Rev. 2000;  CD000485
  • 21 Love R R, Duc N B, Allred D C. et al . Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and Chinese women with operable breast cancer.  J Clin Oncol. 2002;  20 2559-2566
  • 22 Cuzick J. The impact of LHRH agonists on breast cancer recurrence and mortality: an overview of the randomized trials.  Breast Cancer Res Treat. 2006;  100 S10-(abstr.)
  • 23 Gnant M, Greil R, Kubista E. et al . The impact of treatment-induced amenorrhea on survival of premenopausal patients with endocrine-responsive breast cancer: 10-year result of ABCSG‐05 (CMF vs. goserelin+ tamoxifen).  Breast Cancer Res Treat. 2006;  100 S10-(abstr.)
  • 24 Klijn J G, Blamey R W, Boccardo F. et al . Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials.  J Clin Oncol. 2001;  19 343-353
  • 25 Davis A L, Klitus M, Mintzer D M. Chemotherapy-induced amenorrhea from adjuvant breast cancer treatment: the effect of the addition of taxanes.  Clin Breast Cancer. 2005;  6 421-424
  • 26 Colleoni M, Gelber S, Goldhirsch A. et al . Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13 - 93.  J Clin Oncol. 2006;  24 1332-1341
  • 27 Braverman A S, Sawhney H, Tendler A. et al . Pre-menopausal serum estradiol levels may persist after chemotherapy-induced amenorrhea in breast cancer.  Proc ASCO. 2002;  21 42a
  • 28 Baum M, Houghton J, Odling-Smee W. et al . Adjuvant treatment of premenopausal breast cancer with zoladex and tamoxifen: Results from randomized trials by the Cancer Research Campaign (CRC) Breast Cancer Trials Group, The Stockholm Breast Cancer Study Group, The South East Sweden Breast Cancer Group and Gruppo Interdisciplinare Valutazione Intervention Oncologica (GIVIO).  The Breast. 2001;  10 P64
  • 29 Castiglione-Gertsch M, O'Neill A, Price K N. et al . Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial.  J Natl Cancer Inst. 2003;  95 1833-1846
  • 30 Davidson N E, O'Neill A, Vukov A. et al . Effect of chemohormonal therapy in premenopausal node positive, receptor positive breast cancer: An Eastern Cooperative Oncology Group Phase III Intergroup trial (E5188, Int-0101).  J Clin Oncol (Proceedings of ASCO). 2003;  21 15-(abstr)
  • 31 Walshe J M, Denduluri N, Swain S M. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer.  J Clin Oncol. 2006;  24 5769-5779
  • 32 Vanhuyse M, Fournier C, Bonneterre J. Chemotherapy-induced amenorrhea: influence on disease-free survival and overall survival in receptor-positive premenopausal early breast cancer patients.  Ann Oncol. 2005;  16 1283-1288
  • 33 Jonat W, Kaufmann M, Sauerbrei W. et al . Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study.  J Clin Oncol. 2002;  20 4628-4635
  • 34 Borde F, Chapelle-Marcilac I FP, Hery M. et al . Role of chemo-induced amenorrhea in premenopausal, node-positive, operable breast cancer patients: 9-year follow-up results of French Adjuvant Study Group (FASG) data base.  Breast Cancer Res Treat. 2003;  82 30
  • 35 http://www.bqs-qualitaetsreport.de/ 2007
  • 36 Mueller B A, Simon M S, Deapen D. et al . Childbearing and survival after breast carcinoma in young women.  Cancer. 2003;  98 1131-1140
  • 37 Blakely L J, Buzdar A U, Lozada J A. et al . Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence.  Cancer. 2004;  100 465-469
  • 38 Del Mastro L, Venturini M. Fertility preservation strategies for breast cancer patients.  J Clin Oncol. 2006;  24 4220-4221
  • 39 Ives A, Saunders C, Bulsara M. et al . Pregnancy after breast cancer: population based study.  BMJ. 2007;  334 116-167
  • 40 Velentgas P, Daling J R, Malone K E. et al . Pregnancy after breast carcinoma: outcomes and influence on mortality.  Cancer. 1999;  85 2424-2432
  • 41 Goldhirsch A, Glick J H, Gelber R D. et al . Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005.  Ann Oncol. 2005;  16 1569-1583
  • 42 Ataya K, Rao L V, Lawrence E. et al . Luteinizing hormone-releasing hormone agonist inhibits cyclophosphamide-induced ovarian follicular depletion in rhesus monkeys.  Biol Reprod. 1995;  52 365-372
  • 43 Franke H R, Smit W M, Vermes I. Gonadal protection by a gonadotropin-releasing hormone agonist depot in young women with Hodgkin's disease undergoing chemotherapy.  Gynecol Endocrinol. 2005;  20 274-278
  • 44 Blumenfeld Z. Preservation of fertility and ovarian function and minimalization of chemotherapy associated gonadotoxicity and premature ovarian failure: the role of inhibin-A and -B as markers.  Mol Cell Endocrinol. 2002;  187 93-105
  • 45 Bohlmann M K, von Wolff M, Strowitzki T. Comment on the symposium article “Fertility after treatment for Hodgkin's disease”, by Blumenfeld Z, Dann E, Avivi I et al. (Ann Oncol 2002; 13: 138 - 147).  Ann Oncol. 2003;  14 499-500
  • 46 Recchia F, Saggio G, Amiconi G. et al . Gonadotropin-releasing hormone analogues added to adjuvant chemotherapy protect ovarian function and improve clinical outcomes in young women with early breast carcinoma.  Cancer. 2006;  106 514-523
  • 47 Del Mastro L, Catzeddu T, Boni L. et al . Prevention of chemotherapy-induced menopause by temporary ovarian suppression with goserelin in young, early breast cancer patients.  Ann Oncol. 2006;  17 74-78
  • 48 Fox K, Scialla J, Moore H. Preventing chemotherapy-related amenorrhea using leuprolide during adjuvant chemotherapy for early-stage breast cancer.  Proc Am Soc Clin Oncol. 2003;  22 13
  • 49 Urruticoechea A, Walsh G, Rigg A. et al . Ovarian function protection with goserelin during adjuvant chemotherapy in pre-menopausal women with early breast cancer.  Breast Cancer Res Treat. 2004;  88 S229
  • 50 Dargent D, Martin X, Sacchetoni A. et al . Laparoscopic vaginal radical trachelectomy: a treatment to preserve the fertility of cervical carcinoma patients.  Cancer. 2000;  88 1877-1882
  • 51 Ungar L, Palfalvi L, Hogg R. et al . Abdominal radical trachelectomy: a fertility-preserving option for women with early cervical cancer.  BJOG. 2005;  112 366-369
  • 52 Hertel H, Kohler C, Grund D. et al . Radical vaginal trachelectomy (RVT) combined with laparoscopic pelvic lymphadenectomy: prospective multicenter study of 100 patients with early cervical cancer.  Gynecol Oncol. 2006;  103 506-511
  • 53 Shepherd J H, Spencer C, Herod J. et al . Radical vaginal trachelectomy as a fertility-sparing procedure in women with early-stage cervical cancer-cumulative pregnancy rate in a series of 123 women.  BJOG. 2006;  113 719-724
  • 54 Hoeckel M. Die Post-Wertheim-Emanzipation und ‐Evolution der operativen Therapie des Zervixkarzinoms.  Geburtsh Frauenheilk. 2006;  66 729-733
  • 55 Petignat P, Stan C, Megevand E. et al . Pregnancy after trachelectomy: a high-risk condition of preterm delivery. Report of a case and review of the literature.  Gynecol Oncol. 2004;  94 575-577
  • 56 Boss E A, van Golde R J, Beerendonk C C. et al . Pregnancy after radical trachelectomy: a real option?.  Gynecol Oncol. 2005;  99 S152-S156
  • 57 Plante M, Renaud M C, Hoskins I A. et al . Vaginal radical trachelectomy: a valuable fertility-preserving option in the management of early-stage cervical cancer. A series of 50 pregnancies and review of the literature.  Gynecol Oncol. 2005;  98 3-10
  • 58 Leitao Jr. M M, Chi D S. Fertility-sparing options for patients with gynecologic malignancies.  Oncologist. 2005;  10 613-622
  • 59 Rackow B W, Arici A. Endometrial cancer and fertility.  Curr Opin Obstet Gynecol. 2006;  18 245-252
  • 60 Niwa K, Tagami K, Lian Z. et al . Outcome of fertility-preserving treatment in young women with endometrial carcinomas.  BJOG. 2005;  112 317-320
  • 61 Tewari K S, Di Saia P J. Ovulatory failure, fertility preservation and reproductive strategies in the setting of gynecologic and non-gynecologic malignancies.  Eur J Gynaecol Oncol. 2006;  27 449-461
  • 62 Ayhan A, Celik H, Taskiran C. et al . Oncologic and reproductive outcome after fertility-saving surgery in ovarian cancer.  Eur J Gynaecol Oncol. 2003;  24 223-232
  • 63 Boran N, Cil A P, Tulunay G. et al . Fertility and recurrence results of conservative surgery for borderline ovarian tumors.  Gynecol Oncol. 2005;  97 845-851
  • 64 Rao G G, Skinner E N, Gehrig P A. et al . Fertility-sparing surgery for ovarian low malignant potential tumors.  Gynecol Oncol. 2005;  98 263-266
  • 65 Tsai J Y, Saigo P E, Brown C. et al . Diagnosis, pathology, staging, treatment, and outcome of epithelial ovarian neoplasia in patients age < 21 years.  Cancer. 2001;  91 2065-2070
  • 66 Colombo N, Parma G, Lapresa M T. et al . Role of conservative surgery in ovarian cancer: the European experience.  Int J Gynecol Cancer. 2005;  15 206-211
  • 67 Borgfeldt C, Iosif C, Masback A. Fertility-sparing surgery and outcome in fertile women with ovarian borderline tumors and epithelial invasive ovarian cancer.  Eur J Obstet Gynecol Reprod Biol. 2006; 
  • 68 Low J J, Perrin L C, Crandon A J. et al . Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases.  Cancer. 2000;  89 391-398
  • 69 Nishio S, Ushijima K, Fukui A. et al . Fertility-preserving treatment for patients with malignant germ cell tumors of the ovary.  J Obstet Gynaecol Res. 2006;  32 416-421
  • 70 Chan J K, Lin Y G, Loizzi V. et al . Borderline ovarian tumors in reproductive-age women. Fertility-sparing surgery and outcome.  J Reprod Med. 2003;  48 756-760
  • 71 Blumenfeld Z. Gynaecologic concerns for young women exposed to gonadotoxic chemotherapy.  Curr Opin Obstet Gynecol. 2003;  15 359-370

Prof. Dr. med. B. Gerber

Universitäts-Frauenklinik am Klinikum Südstadt

Südring 81

18059 Rostock

eMail: bernd.gerber@med.uni-rostock.de

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