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Fertility Preservation in Women—A Practical Guide To Arch Gynecol Obstet (2011) 284:427–435 DOI 10.1007/s00404-011-1874-1 GYNECOLOGIC ONCOLOGY Fertility preservation in women—a practical guide to preservation techniques and therapeutic strategies in breast cancer, Hodgkin’s lymphoma and borderline ovarian tumours by the fertility preservation network FertiPROTEKT Michael von Wolff • Markus Montag • Ralf Dittrich • Dominik Denschlag • Frank Nawroth • Barbara Lawrenz Received: 8 November 2010 / Accepted: 2 March 2011 / Published online: 24 March 2011 Ó The Author(s) 2011. This article is published with open access at Springerlink.com Abstract individual use of fertility preservation methods for various Purpose Fertility preservation methods are playing an indications such as breast cancer, Hodgkin’s lymphoma increasing role in women up to the age of 40 years because and borderline ovarian tumours are given. of rising survival rates in those affected by cancer. How- Results Various options such as ovarian stimulation and ever, balanced practical recommendations concerning all cryopreservation of unfertilised or fertilised oocytes, relevant fertility preservation, to support doctors in coun- cryopreservation and transplantation of ovarian tissue, selling and treating patients, are still rare. GnRH-agonist administration and transposition of the Methods These recommendations were prepared by the ovaries can be offered. All the techniques can be performed network FertiPROTEKT (http://www.fertiprotect.eu), a alone or in combination within a maximum of 2 weeks collaboration of around 70 centres in Germany, Switzer- with low risk and different success rates. land and Austria. The recommendations were developed by Conclusions Fertility preservation in women has become specialists in reproductive medicine, reproductive biology an option with realistic chances to become pregnant after and oncology, which gave a comprehensive overview of all cytotoxic therapies. The information provided allows a named techniques as well as their benefits and risks. Fur- well balanced and realistic counselling and treatment. thermore, practice-orientated recommendations for the Keywords Cancer Á Fertility preservation Á Oocytes Á Ovarian tissue Cryopreservation GnRH agonists In the name of all members of the network FertiPROTEKT. Á Á M. von Wolff (&) Department of Gynaecological Endocrinology and Reproductive Introduction Medicine, University Women’s Hospital, Effingerstrasse 102, 3010 Bern, Switzerland e-mail: [email protected] Increasing survival rates in patients affected by oncological disease and advances in reproductive medicine have led to M. Montag the development and increasing use of various fertility Department of Gynaecological Endocrinology and Reproductive preservation techniques. Over the last few years, several Medicine, University Women’s Hospital, Bonn, Germany techniques have been particularly favoured despite insuf- R. Dittrich ficient data and others have not been recommended. University Women’s Hospital, Erlangen, Germany Meanwhile however, improving data and optimisation of the available techniques have allowed a realistic portrayal D. Denschlag Hochtaunus-Kliniken, Bad Homburg, Germany of the efficacy and risks of the most commonly used methods as well as recommendations for the use of the F. Nawroth techniques alone or in combination. Many recommenda- Hormon- und Pra¨natalzentrum, Hamburg, Germany tions can be found in the literature on fertility protection; B. Lawrenz however, there is no current publication which objectively University Women’s Hospital, Tuebingen, Germany considers all the established techniques [1, 2]. Furthermore, 123 428 Arch Gynecol Obstet (2011) 284:427–435 most work focuses only on the techniques as such or on finally a discussion of their use in breast cancer, Hodg- their relevance in various disease states without consider- kin’s lymphoma and borderline ovarian tumours ing both aspects and connecting them with one another. (Tables 1, 2, 3 and 4). Recommendations from the FertiPROTEKT Network [3], described below, were formulated for clinical practice in such a way that not only the techniques are objectively represented, but also recommendations for their use in General recommendations clinical practice for the commonest oncological diseases are also given. The recommendations, developed by spe- • All women between the ages of ca. 14 and 40 years cialists in reproductive medicine and reproductive biolo- who receive chemotherapy which could lead to a sig- gists as well as oncologists, avoid a detailed listing of all nificant chance of disruption to their ovarian function the underlying work, and rather summarise their key should be counselled by a doctor trained in reproduc- messages and reinforce them with information from current tive medicine on fertility preservation methods, in publications or review articles. This concept allows a agreement with the responsible oncologists. comprehensive and practice-orientated description of a • All applicable methods should be included in the complex topic and an application for specialists in repro- counselling. ductive medicine and oncologists. • All counselling and treatments, including complications The general recommendations for the counselling on which occur, should be documented in the records. and use of fertility preservation methods are presented • Performing fertility preservation techniques, i.e. due to first in the following review (Fig. 1), followed by the the postponement of a cytotoxic therapy, must not techniques, a description of their efficacy and risks, and affect the efficacy of the oncological regimen. Fig. 1 Simplified regimen for Fertility preservation of post pubertal women the use of fertility preservation procedures. It should be noted that the choice of method also Radiation of the Chemotherapy can be postponed Chemotherapy can pelvis be postponed by <2 depends on the patient’s age, by 2 weeks their prognosis, the toxicity of weeks the chemotherapy and the individual wishes of the patient Ovarian Tumor not estrogen Tumor estrogen Cryopreservation of and their partner transposition dependant dependant ovarian tissue and /or and/or Ovarian stimulation Ovarian stimulation Cryopreservation of and cryopreservation and cryopreservation GnRH-agonists ovarian tissue of unfertilized or of unfertilized or and /or fertilized oocytes fertilized oocytes aromatase inhibitors Ovarian stimulation and / or and /or and Cryopreservation of cryopreservation of ovarian tissue Cryopreservation of unfertilized or ovarian tissue fertilized oocytes and/or and/or GnRH-agonists GnRH-agonists Table 1 Breast cancer: chemotherapy-associated amenorrhoea rate (A = doxorubicin; C = cyclophosphamide; E = epirubicin; F = 5-fluo- rouraci; M = methotrexate (modified according to [39]) Age (years) Chemotherapy Rate of amenorrhoea (%) [40 6 9 CMF, 6 9 FEC, 6 9 FAC [ 80 (High risk) \40 High-dose EC 30–39 6 9 CMF, 6 9 FEC, 6 9 FAC 20–80 (Moderate risk) [40 4 9 AC \30 6 9 CMF, 6 9 FEC, 6 9 FAC \20 (Low risk) \40 4 9 AC Insufficient data: taxanes, monoclonal antibodies, avastinÒ (bevacizumab), lapatinib, herceptinÒ (trastuzumab) and gemzarÒ (gemcitabine) 123 Arch Gynecol Obstet (2011) 284:427–435 429 Table 2 Breast cancer: fertility preservation procedures depending on hormone receptor status and oncological treatment plan in women with a medium to high risk of amenorrhoea Adjuvant situation (fertility preservation after Neoadjuvant situation (fertility preservation surgery and before chemotherapy) before chemotherapy and before surgery) Hormone Hormone Hormone Hormone receptor receptor receptor receptor negative positive negative positive Hormonal stimulation and ? (?)(?) - cryopreservation (± combination with (± combination with of unfertilised and fertilised oocytes letrozole) letrozole) Cryopreservation of ovarian tissue ?? ? ? Combination of hormonal stimulation ? (?)(?) - and cryopreservation of oocytes (± combination with (± combination with and ovarian tissue letrozole) letrozole) GnRH-agonists ? (-) ? (-) Description of ovarian stimulation Table 3 Hodgkin’s lymphoma—Chemotherapy-associated amenor- rhoea rate (A = adriamycin; B = bleomycin; C = cyclophospha- mide; E = etoposide; O = oncovin; P = procarbazine and • Starting stimulation during menstruation: perform a prednisone V = vinblastine) modified according to [40]) classic GnRH-antagonist protocol, as this is associated with a lower risk of ovarian hyperstimulation syndrome Age (years) Chemotherapy Rate of amenorrhoea (OHSS) [4] (%) • Starting stimulation in other cycle phases: GnRH- antagonist immediately and simultaneously start C30 2 9 ABVD (HD 7, arm B) 0 administering recombinant follicle stimulating hor- \ 30 5.6 mone (FSH) [5] C30 2 9 COPP/ABVD (HD 8) 12.2 • Induction of ovulation in the case of impending OHSS \30 3.5 with triptorelin 0.2 mg [6] C30 4 9 COPP/ABVD (HD 9 A) 53.3 • In the case of estrogen-dependent tumours, stimulation \30 23.5 can be combined with letrozole 5 mg daily [7], which is C30 8 9 BEACOPP (HD 9, arm B) 42.1 administered at the same time as the gonadotrophin. \30 11.8 C30 8 BEACOPP escalated (HD 9, Arm C) 70.4 \30 40.4 Description of cryopreservation of fertilised and unfertilised oocytes To reduce the risk of fertilisation failure, intracytoplasmic Fertility protection techniques sperm injection (ICSI) should be considered, with only jus- tifiable exceptions, and independent of the spermiogram. Ovarian stimulation and cryopreservation Unfertilised oocytes are preserved by slow freezing or of unfertilised and fertilised oocytes vitrification.
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