CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2018; 78(06): 567-584
DOI: 10.1055/a-0611-5549
GebFra Science
Guideline/Leitlinie
Georg Thieme Verlag KG Stuttgart · New York

Fertility Preservation for Patients with Malignant Disease. Guideline of the DGGG, DGU and DGRM (S2k-Level, AWMF Registry No. 015/082, November 2017) – Recommendations and Statements for Girls and Women

Artikel in mehreren Sprachen: English | deutsch
Ralf Dittrich
1  Frauenklinik, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
,
Sabine Kliesch
2  Centrum für Reproduktionsmedizin und Andrologie, Universitätsklinik Münster, Münster, Germany
,
Andreas Schüring
3  Frauenklinik, Universitätsklinikum Münster, Münster, Germany
,
Magdalena Balcerek
4  Pädiatrie mit Schwerpunkt Onkologie und Hämatologie, Charité Berlin, Berlin, Germany
,
Dunja M. Baston-Büst
5  Frauenklinik, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
,
Ramona Beck
6  Frauenselbsthilfe nach Krebs e. V., Germany
,
Matthias W. Beckmann
1  Frauenklinik, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
,
Karolin Behringer
7  Hämatologie und Onkologie, Universitätsklinikum Köln, Köln, Germany
,
Anja Borgmann-Staudt
4  Pädiatrie mit Schwerpunkt Onkologie und Hämatologie, Charité Berlin, Berlin, Germany
,
Wolfgang Cremer
8  Praxis für Frauenheilkunde Hamburg, Hamburg, Germany
,
Christian Denzer
9  Kinder- und Jugendmedizin, Universitätsklinikum Ulm, Ulm, Germany
,
Thorsten Diemer
10  Klinik und Poliklinik für Urologie, Kinderurologie und Andrologie, Universitätsklinikum Gießen, Gießen, Germany
,
Almut Dorn
11  Praxis für Gynäkologische Psychosomatik, Hamburg, Germany
,
Tanja Fehm
5  Frauenklinik, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
,
Rüdiger Gaase
12  Gemeinschaftspraxis für Frauenheilkunde, Worms, Germany
,
Ariane Germeyer
13  Frauenklinik, Universitätsklinikum Heidelberg, Heidelberg, Germany
,
Kristina Geue
14  Medizinische Psychologie und Medizinische Soziologie, Universitätsklinikum Leipzig, Leipzig, Germany
,
Pirus Ghadjar
15  Radioonkologie und Strahlentherapie, Charité Berlin, Berlin, Germany
,
Maren Goeckenjan
16  Frauenklinik, Universitätsklinikum Dresden, Dresden, Germany
,
Martin Götte
3  Frauenklinik, Universitätsklinikum Münster, Münster, Germany
,
Dagmar Guth
17  Praxis für Frauenheilkunde Plauen, Plauen, Germany
,
Berthold P. Hauffa
18  Kinderendokrinologie, Universitätsklinikum Essen, Essen, Germany
,
Ute Hehr
19  Zentrum für Humangenetik, Universitätsklinikum Regensburg, Regensburg, Germany
,
Franc Hetzer
20  Chirurgisches Departement, Spital Linth, Uznach, Switzerland
,
Jens Hirchenhain
5  Frauenklinik, Universitätsklinikum Düsseldorf, Düsseldorf, Germany
,
Wilfried Hoffmann
21  Hamm-Kliniken GmbH Badenweiler, Badweiler, Germany
,
Beate Hornemann
22  Universitäts KrebsCentrum UCC Dresden, Dresden, Germany
,
Andreas Jantke
23  Kinderwunsch Ärzte Berlin, Berlin, Germany
,
Heribert Kentenich
24  Fertility Center Berlin, Berlin, Germany
,
Ludwig Kiesel
16  Frauenklinik, Universitätsklinikum Dresden, Dresden, Germany
,
Frank-Michael Köhn
25  Andrologicum München, München, Germany
,
Matthias Korell
26  Frauenklinik, Johanna Etienne Klinikum Neuss, Neuss, Germany
,
Sigurd Lax
27  Institut für Pathologie, LKH Graz Süd-West, Graz, Austria
,
Jana Liebenthron
28  Gynäkologische Endokrinologie und Reproduktionsmedizin, Universitätsklinikum Bonn, Bonn, Germany
,
Michael Lux
1  Frauenklinik, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
,
Julia Meißner
29  Hämatologie, Onkologie und Rheumatologie, Universitätsklinikum Heidelberg, Heidelberg, Germany
,
Oliver Micke
30  Strahlentherapie und Radioonkologie, Franziskus Hospital Bielefeld, Bielefeld, Germany
,
Najib Nassar
31  Praxis für Frauenheilkunde, Essen, Germany
,
Frank Nawroth
32  Facharzt-Zentrum für Kinderwunsch, Pränatale Medizin, Endokrinologie und Osteologie, amedes MVZ Hamburg GmbH, Hamburg, Germany
,
Verena Nordhoff
2  Centrum für Reproduktionsmedizin und Andrologie, Universitätsklinik Münster, Münster, Germany
,
Falk Ochsendorf
33  Andrologie, Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt, Frankfurt, Germany
,
Patricia G. Oppelt
1  Frauenklinik, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
,
Jörg Pelz
34  Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Würzburg, Würzburg, Germany
,
Beate Rau
35  Onkologische Chirurgie, Charité Berlin, Berlin, Germany
,
Nicole Reisch
36  Endokrinologie, Universitätsklinikum München, München, Germany
,
Dorothea Riesenbeck
37  Praxis für Strahlentherapie, Recklinghausen, Germany
,
Stefan Schlatt
2  Centrum für Reproduktionsmedizin und Andrologie, Universitätsklinik Münster, Münster, Germany
,
Annekathrin Sender
14  Medizinische Psychologie und Medizinische Soziologie, Universitätsklinikum Leipzig, Leipzig, Germany
,
Roxana Schwab
38  Frauenklinik, Universitätsklinikum Mainz, Mainz, Germany
,
Friederike Siedentopf
39  Brustzentrum, Martin-Luther-Krankenhaus, Paul Gerhardt Diakonie, Berlin-Wilmersdorf, Germany
,
Petra Thorn
40  Praxis für psychosoziale Kinderwunschberatung, Paar- und Familientherapie, Mörfelden-Walldorf, Germany
,
Steffen Wagner
41  Frauenärzte Saarbrücken-West, Saarbrücken, Germany
,
Ludwig Wildt
42  Gynäkologische Endokrinologie und Reproduktionsmedizin, Universitätsklinikum Innsbruck, Innsbruck, Austria
,
Pauline Wimberger
16  Frauenklinik, Universitätsklinikum Dresden, Dresden, Germany
,
Tewes Wischmann
43  Medizinische Psychologie, Universitätsklinikum Heidelberg, Heidelberg, Germany
,
Michael von Wolff
44  Gynäkologische Endokrinologie und Reproduktionsmedizin, Universitäts-Spital Bern, Bern, Switzerland
,
Laura Lotz
1  Frauenklinik, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
› Institutsangaben
Weitere Informationen

Correspondence/Korrespondenzadresse

Prof. Dr. rer. nat. Ralf Dittrich
Frauenklinik
Universitätsklinikum Erlangen
Universitätsstraße 21 – 23
91054 Erlangen

Publikationsverlauf

received 20. März 2018
revised 15. April 2018

accepted 17. April 2018

Publikationsdatum:
25. Juni 2018 (online)

 

Abstract

Aim The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline.

Methods This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40).

Recommendations The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patientʼs personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities.


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I  Guideline Information

Information on the guidelines program of the DGGG, OEGGG and SGGG is provided at the end of the article.

Citation format

Fertility Preservation for Patients with Malignant Disease. Guideline of the DGGG, DGU and DGRM (S2k-Level, AWMF Registry No. 015/082, November 2017) – Recommendations and Statements for Girls and Women. Geburtsh Frauenheilk 2018; 78: 567–584


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Guideline documents

The complete long version of the guideline in German, a PDF slideshow for PowerPoint presentations and a summary of the conflicts of interest of all authors are available on the homepage of the AWMF: http://www.awmf.org/leitlinien/detail/ll/015-082.html


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Guideline authors

The following professional and scientific societies/working groups/organizations/associations stated the interest in contributing to the compilation of the guideline text and participating in the consensus conference and nominated representatives to attend the consensus conference ([Table 1]).

Table 1 Authors and representativity of the guideline group: participation of the target user group.

Author

Mandate holder

DGGG working group/AWMF/non-AWMF professional society/organization/association

Dr. med. Magdalena Balcerek

Society for Pediatric Oncology and Hematology [Gesellschaft für Pädiatrische Onkologie und Hämatologie e. V.] (GPOH)

Ramona Beck

Self-help Group for Women after Cancer [Frauenselbsthilfe nach Krebs e. V.]

Prof. Dr. med. Matthias W. Beckmann

Expert

Dr. med. Karolin Behringer

Working Group for Internal Oncology [Arbeitsgemeinschaft Internistische Onkologie] (AIO); German Society for Hematology and Medical Oncology [Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e. V.] (DGHO)

Prof. Dr. med. Anja Borgmann-Sta[udt

German Society for Pediatric and Adolescent Medicine [Deutsche Gesellschaft für Kinder- und Jugendmedizin e. V.] (DGKJ); Society for Pediatric Oncology and Hematology [Gesellschaft für Pädiatrische Onkologie und Hämatologie e. V.] (GPOH)

Dr. rer. nat. Dunja M. Baston-Büst

German Society of Reproductive Medicine [Deutsche Gesellschaft für Reproduktionsmedizin e. V.] (DGRM)

Dr. med. Wolfgang Cremer

Professional Association of Gynecologists [Berufsverband der Frauenärzte e. V.] (BVF)

Dr. med. Christian Denzer

German Society for Pediatric Endocrinology and Diabetes [Deutsche Gesellschaft für Kinderendokrinologie und -diabetologie e. V.] (DGKED)

PD Dr. med. Thorsten Diemer

German Society of Urology [Deutsche Gesellschaft für Urologie e. V.] (DGU)

Prof. Dr. rer. nat. Ralf Dittrich[

German Society of Gynecology and Obstetrics [Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e. V.] (DGGG)

Dipl.-Psych. Dr. phil. Almut Dorn

German Society for Psychiatry, Psychotherapie and Psychosomatics [Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde e. V.] (DGPPN)

Prof. Dr. med. Tanja Fehm

Gynecologic Oncology Working Group [Arbeitsgemeinschaft Gynäkologische Onkologie e. V.] (AGO)

Dr. med. Rüdiger Gaase

Professional Association of Gynecologists (BVF)

Prof. Dr. med. Ariane Germeyer

German Society for Gynecologic Endocrinology and Reproductive Medicine [Deutsche Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin e. V.] (DGGEF)

Dr. rer. med. Kristina Geue

Psycho-Oncology Working Group [Arbeitsgemeinschaft für Psychoonkologie e. V.] (PSO)

PD Dr. med. Pirus Ghadjar

German Society of Radio-Oncology [Deutsche Gesellschaft für Radioonkologie e. V.] (DEGRO)

Dr. med. Maren Goeckenjan

German Society for Gynecologic Endocrinology and Reproductive Medicine (DGGEF)

Prof. Dr. rer. nat. Martin Götte

German Society for Endocrinology [Deutsche Gesellschaft für Endokrinologie e. V.] (DGE)

Dr. med. Dagmar Guth

Professional Association of Practice-based Gynecologic Oncologists in Germany [Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e. V.] (BNGO)

Prof. Dr. med. Berthold P. Hauffa

German Society for Pediatric Endocrinology and Diabetes (DGKED)

Prof. Dr. med. Ute Hehr

German Society of Human Genetics [Deutsche Gesellschaft für Humangenetik e. V.] (GfH)

Prof. Dr. med. Franc Hetzer

German Society of Coloproctology [Deutsche Gesellschaft für Koloproktologie e. V.] (DGK)

Dr. rer. nat. Jens Hirchenhain

German Society of Human Reproductive Biology [Arbeitsgemeinschaft Reproduktionsbiologie des Menschen e. V.] (AGRBM)

Dr. med. Wilfried Hoffmann

Working Group for Supportive Care in Oncology, Rehabilitation and Social Medicine [Arbeitsgemeinschaft Supportive Maßnahmen in der Onkologie, Rehabilitation und Sozialmedizin e. V.] (ASORS)

Dipl.-Psych. Beate Hornemann

Psycho-Oncology Working Group (PSO)

Dr. med. Andreas Jantke

Federal Association of Reproductive Medicine Centers in Germany [Bundesverband Reproduktionsmedizinischer Zentren Deutschland e. V.] (BRZ)

Prof. Dr. med. Heribert Kentenich

German Society of Psychosomatic Obstetrics and Gynecology [Deutsche Gesellschaft für Psychosomatische Frauenheilkunde und Geburtshilfe e. V.] (DGPFG)

Prof. Dr. med. Frank-Michael Köhn

German Society of Andrology [Deutsche Gesellschaft für Andrologie e. V.] (DGA); German Society for Sexual Medicine, Sexual Therapy and Sexual Science [Deutsche Gesellschaft für Sexualmedizin, Sexualtherapie und Sexualwissenschaft e. V.] (DGSMTW)

Prof. Dr. med. Ludwig Kiesel

German Society for Endocrinology (DGE)

Prof. Dr. med. Sabine Kliesch

German Society of Urology (DGU); Working Group on Urologic Oncology [Arbeitsgemeinschaft Urologische Onkologie e. V.] (AUO)

Prof. Dr. med. Matthias Korell

Gynecologic Endoscopy Working Group [Arbeitsgemeinschaft Gynäkologische Endoskopie e. V.] (AGE)

Prof. Prim. Dr. Sigurd Lax

German Society of Pathology [Deutsche Gesellschaft für Pathologie e. V.] (DGP); Federal Association of German Pathologists [Bundesverband Deutscher Pathologen e.V] (BVDP)

Dr. rer. nat. Jana Liebenthron

FertiPROTEKT Network

Dr. med. Laura Lotz

Guidelines secretary

Prof. Dr. med. Michael Lux

German Society for Senology [Deutsche Gesellschaft für Senologie e. V.] (DGS)

Dr. med. Julia Meißner

Internal Oncology Working Group [Arbeitsgemeinschaft Internistische Onkologie] (AIO); German Society for Hematology and Medical Oncology [Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e. V.] (DGHO)

Prof. Dr. med. Oliver Micke

AG PRIo of the DKG [German Cancer Society]

Najib Nassar

Federal Association of Reproductive Medicine Centers in Germany (BRZ)

Prof. Dr. med. Frank Nawroth

FertiPROTEKT Network

PD Dr. rer. nat. Verena Nordhoff

Human Reproductive Biology Working Group [Arbeitsgemeinschaft Reproduktionsbiologie des Menschen e. V.] (AGRBM)

Prof. Dr. med. Falk Ochsendorf

German Dermatology Society [Deutsche Dermatologische Gesellschaft e. V.] (DDG)

PD Dr. Patricia G. Oppelt

Pediatric and Adolescent Gynecology Working Group [Arbeitsgemeinschaft Kinder- und Jugendgynäkologie e. V.] (AG)

Prof. Dr. med. Jörg Pelz

German Society for General and Visceral Surgery [Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie e. V.] (DGAV)

Prof. Dr. med. Beate Rau

German Society for General and Visceral Surgery (DGAV)

PD Dr. med. Nicole Reisch

German Society of Internal Medicine [Deutsche Gesellschaft für Innere Medizin e. V.] (DGIM)

Dr. med. Dorothea Riesenbeck

Working Group for Supportive Care in Oncology, Rehabilitation and Social Medicine (ASORS); German Society of Radio-Oncology (DEGRO)

Prof. Dr. rer. nat. Stefan Schlatt

Clinical Research Group for Reproductive Medicine [Klinische Forschergruppe für Reproduktionsmedizin e. V.]

PD Dr. Andreas Schüring

German Society of Reproductive Medicine (DGRM)

Dr. med. Roxana Schwab

Expert

Dip.-Psych. Annekathrin Sender

Expert

PD Dr. med. Friederike Siedentopf

German Society of Psychosomatic Obstetrics and Gynecology (DGPFG)

Dr. phil. Petra Thorn

Infertility Counseling Network Germany [Beratungsnetzwerk Kinderwunsch Deutschland e. V.] (BKiD)

Dr. med. Steffen Wagner

Professional Association of Practice-based Gynecologic Oncologists in Germany (BNGO)

Prof. Dr. med. Ludwig Wildt

German Society for Endocrinology (DGE); Austrian Society of Gynecology and Obstetrics [Österreichische Gesellschaft für Gynäkologie und Geburtshilfe e. V.] (OEGGG)

Prof. Dr. med. Pauline Wimberger

Expert

PD Dr. sc. hum. Tewes Wischmann, Dipl.-Psych.

Infertility Counseling Network Germany (BKiD)

Prof. Dr. med. Michael von Wolff

Swiss Society of Gynecology and Obstetrics [Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe] (SGGG)


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Abbreviations

ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine
AC: doxorubicin, cyclophosphamide
ALL: acute lymphoblastic leukemia
AMH: anti-Müllerian hormone
AML: acute myeloid leukemia
ART: assisted reproductive technologies
BEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone
BOT: borderline tumor
CAF: cyclophosphamide, adriamycin, fluorouracil
CEF: cyclophosphamide, epirubicin, 5-flourouracil
ChlVPP/EVA hybrid COPP: chlorambucil, vinblastine, procarbazine, prednisone/
etoposide, vincristine, doxorubicin
CHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone
CI: confidence interval
CMF: cyclophosphamide, methotrexate, 5-fluorouracil
CML: chronic myelogenous leukemia
CVP: cyclophosphamide, vincristine, prednisone
DMSO: dimethyl sulfoxide
EC: epirubicin, cyclophosphamide
ESD: effective sterilizing dose
FOLFOX: folinic acid (leucovorin), 5-fluorouracil, oxaliplatin
GnRH: gonadotropin-releasing hormone
GnRHa: gonadotropin-releasing hormone agonist
Gy: Gray
HL: Hodgkinʼs lymphoma
MVPP: mustine, vinblastine, procarbazine, prednisolone
NHL: non-Hodgkinʼs lymphoma
OR: odds ratio
POI: premature ovarian insufficiency
RR: relative risk
SCT: stem cell transplantation
TAC: paclitaxel (taxol), doxorubicin (adriamycin), cyclophosphamide
TKI: tyrosine kinase inhibitors
 


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II  Guideline Application

Purpose and Objectives

The purpose of this guideline is to provide recommendations for action with regard to counseling and fertility preservation for prepubertal girls and women of reproductive age with oncologic disease which take account of the patientsʼ personal circumstances and risk profile. The aim is to increase the rate of successful pregnancies after completing oncologic therapy and to improve the patientsʼ quality of life.


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Targeted areas of patient care

  • Outpatient care

  • Inpatient care

  • Semi-residential care


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Target patient groups

The guideline is aimed at all prepubertal girls and patients of reproductive age who require gonadotoxic treatment for malignant disease.


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Target user group/target audience

This guideline is aimed at all physicians and medical professionals involved in the care of patients who require gonadotoxic therapy.

The principal among these are: gynecologists, reproductive medicine physicians, andrologists, urologists, oncologists, radio-oncologists, general practitioners, pediatricians, pathologists, psycho-oncologists.


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Adoption of the guideline and period of validity

This guideline is valid from November 1, 2017 to October 31, 2020. Because of the contents of the guideline, this period of validity is only an estimate. If there are important changes to the evidence, then amendments to the guideline will be published before the period of validity has expired, once the new evidence has been carefully reviewed in accordance with the methodology of the AWMF.


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III  Methodology

Basic principles

The methodology used to prepare this guideline is determined by the class to which the guideline is assigned. The AWMF Guidance Manual (version 1.0) has set out the respective rules and regulations for the classification of guidelines. Guidelines are differentiated into lowest (S1), intermediate (S2) and highest (S3) class. The lowest class is defined as a summary of recommendations for action compiled by a non-representative group of experts. In 2004 the S2 class was divided into two subclasses: a systematic evidence-based subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class combines both approaches.

This guideline is classified as: S2k


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Grading of recommendations

While the description of the quality of the evidence (strength of evidence) serves as an indication for the robustness of the publicized data and therefore expresses the extent of certainty/uncertainty about the data, the classification of the level of recommendation reflects the result of weighing up the desirable and adverse consequences of alternative approaches.

A grading of the evidence and of the recommendations is not envisaged for S2k-level guidelines. The level of recommendation is differentiated by syntax, not by symbols. The syntax used to grade the level of recommendation is described in the background text ([Table 2]).

Table 2 Grading of recommendations.

Description of level of recommendation

Syntax

Strong recommendation, highly binding

must/must not

Recommendation, moderately binding

should/should not

Open recommendation, not binding

may/may not


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Statements

Expert statements included in this guideline which are not recommendations for action but simple statements of fact are referred to as Statements. It is not possible to provide a level of evidence for these statements.


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Achieving consensus and strength of consensus

As part of structured consensus-based decision-making (S2k/S3 level), authorized participants present at consensus sessions vote on draft Statements and Recommendations. Discussions at the sessions can lead to significant changes in the wording of Statements and Recommendations. The extent of agreement, which depends on the number of participants, is then determined at the end of the session ([Table 3]).

Table 3 Classification on extent of agreement following consensus-based decision-making.

Symbol

Strength of consensus

Extent of agreement in percent

+++

Strong consensus

> 95% of participants agree

++

Consensus

> 75 – 95% of participants agree

+

Majority agreement

> 50 – 75% of participants agree

No consensus

< 50% of participants agree


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Expert consensus

As the name implies, this term refers to consensus decisions taken with regard to specific Recommendations/Statements without a previous systematic search of the literature (S2k) or when evidence is lacking (S2e/S3). The term “expert consensus” (EC) used here is synonymous with terms used in other guidelines such as “good clinical practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation is graded as previously described in the chapter “Grading of recommendations”; the strength of consensus is only indicated semantically (“must”/“must not” or “should”/“should not” or “may”/“may not”) with no use of symbols.


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IV  Guideline

Statements and Recommendations on fertility preservation for girls and women with oncologic disease are presented below.

1  Introduction to Fertility Protection for Persons Diagnosed with Oncologic Disease

1.2  Importance and problems of fertility protection for persons diagnosed with cancer

Oncologic therapies often lead to partial or complete impairment of gonadal function in both men and women along with the potential loss of germ cells. Faced by the impact of a life-threatening disease, subsequent infertility may appear to be a minor issue for non-affected persons. For many of the patients themselves, however, premature ovarian insufficiency or sterility is a very stressful situation for both the affected patient and their partner [2], [3].

Consensus-based Recommendation 1.R1

Expert consensus

Strength of consensus ++

Assessing the risk of possible infertility and the choice of method(s) for fertility preservation must be done by an interdisciplinary panel and discussed with the patient in good time before the start of oncologic therapy.

Consensus-based Statement 1.S1

Expert consensus

Strength of consensus +++

Counseling about concepts to preserve fertility must be an integral part of every patientʼs oncologic treatment and must take account of the patientʼs personal circumstances, recommended oncologic therapy and individual risk profile.


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2  Causes of Gonadal Toxicity in Women

2.1  Gonadal damage from surgery

Depending on the extent of radical surgery, gynecologic oncologic disease can result in sterility following complete or partial removal of the uterus and/or ovaries. Fertility-preserving surgery for various tumor entities is discussed in Chapter 4.1 of the long version of the guideline.


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2.2  Gonadal toxicity from chemotherapy

The gonadal toxicity of individual chemotherapeutic drugs depends on their mechanism of action, the administered dose, the duration of therapy, the way in which therapy is administered, concomitant therapeutic treatments such as simultaneous radiotherapy or ovary-removal surgery, the patientʼs age, and the patientʼs individual disposition ([Table 4]).

Table 4 Ovarian toxicity of different chemotherapeutic drugs (modified from [4], [5]).

Risk

Regimen/Substance

High risk (> 80% risk of permanent amenorrhea)

  • CMF, CEF, CAF, TAC × 6 for women aged ≥ 40 years

  • Conditioning for stem cell transplantation (particularly alkylating agent-based myeloablative conditioning with busulfan, cyclophosphamide, melphalan)

  • BEACOPP × 6 – 8 for women aged > 35 years

Intermediate risk (40 – 60% risk of permanent amenorrhea)

  • CMF, CEF, CAF, TAC × 6 for women aged 30 – 39 years

  • AC × 4 for women aged ≥ 40 years

  • AC or EC × 4 → taxane

  • BEACOPP × 6 – 8 for women aged 25 – 35 years

  • CHOP × 6 for women aged ≥ 35 years

  • Standard therapies for bone and soft tissue sarcomas

Low risk (< 20% risk of permanent amenorrhea)

  • CMF, CEF, CAF, TAC × 6 for women aged ≤ 30 years

  • AC × 4 for women aged ≤ 40 years

  • BEACOPP × 6 – 8 for women aged < 25 years

  • ABVD × 2 – 4

  • CHOP × 6 for women aged < 35 years

  • CVP

  • AML-type therapy (anthracyclines/
    cytarabine)

  • ALL-type therapy (multi-agent)

  • FOLFOX for women aged ≤ 40 years

Very low or no risk of permanent amenorrhea

  • Methotrexate

  • Fluorouracil

  • Vincristine

Consensus-based Statement 2.R2

Expert consensus

Strength of consensus +++

Women scheduled to receive a potentially gonadotoxic dose of chemotherapeutic drugs must be informed about the risk of ovarian insufficiency and about methods to preserve fertility.

Consensus-based Statement 2.S3

Expert consensus

Strength of consensus +++

The negative impact of the gonadal toxicity of chemotherapies increases with patient age. Not all patients in a specific age group who receive therapy according to a defined regimen will develop the same fertility disorder.


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2.3  Gonadal toxicity from radiotherapy

2.3.1  Ovarian radiation damage

([Table 5])

Table 5 Radiotoxicity and ovarian insufficiency (modified from [6]).

Effective sterilizing dose (ESD)

Ovarian radiation dose (Gy)

No relevant effect

0.6

No relevant effect at < 40 years

1.5

0 years

20.3

10 years

18.4

20 years

16.5

30 years

14.3

40 years

6

Consensus-based Statement 2.S4

Expert consensus

Strength of consensus +++

Whether women develop ovarian insufficiency depends on the radiation dose, the age when the patient was exposed to radiation and the volume of irradiated ovarian tissue.

Consensus-based Recommendation 2.R3

Expert consensus

Strength of consensus +++

Patients who are scheduled to receive radiotherapy which will also irradiate the anatomical area of the ovaries must be informed about the risk of ovarian damage and must be made aware of methods which could preserve their fertility.


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2.3.2  Tubal radiation damage

Radiogenic tubal changes can lead to a loss of function, resulting in limited fertility. Extrauterine pregnancies and their associated subsequent complications can occur, even if ovarian and uterine function have been preserved. Nothing is known about tubal tolerance doses.


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2.3.3  Uterine radiation damage

In contrast to chemotherapy, radiotherapy can affect uterine function in addition to affecting the ovaries. Here again, the effect depends on the dose; the dose-response relationship has not yet been clearly defined [7].

Consensus-based Statement 2.S5

Expert consensus

Strength of consensus +++

Irradiation of the uterus can lead to uterine and tubal sterility and to increased pregnancy risks such as preterm birth, miscarriage and lower birth weight of the infant.


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2.3.4  Radiation damage to the hypothalamic/hypophyseal axis

Consensus-based Recommendation 2.R4

Expert consensus

Strength of consensus +++

Before undergoing radiotherapy of the head region, patients must be informed about the risk of damaging the hypothalamic/hypophyseal axis and the consequences of this damage.


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2.4  Gonadal toxicity through immunotherapy or targeted therapies

Consensus-based Recommendation 2.R5

Expert consensus

Strength of consensus +++

Women receiving therapy with bevacizumab should be informed about the risk of ovarian insufficiency and about methods to preserve fertility.

Consensus-based Recommendation 2.R2

Expert consensus

Strength of consensus +++

Patients who receive immunotherapy or targeted therapy should be informed about the unclear risk of ovarian insufficiency and about methods to preserve fertility.


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2.5  Gonadal toxicity from endocrine therapies

Consensus-based Statement 2.S6

Expert consensus

Strength of consensus +++

Data on gonadal toxicity of tamoxifen are limited and inconsistent; there are no data on the possible effects of aromatase inhibitors combined with GnRH agonists. A gonadotoxic effect is unlikely.

Consensus-based Statement 2.S7

Expert consensus

Strength of consensus +++

The most important fertility-reducing effect of endocrine therapy used to treat breast cancer is the length of the treatment, as it postpones the time when the patient can have children to a stage in life when patient has reduced ovarian reserve.

Consensus-based Recommendation 2.R7

Expert consensus

Strength of consensus ++

Ways of protecting fertility such as cryopreservation of fertilized and/or unfertilized oocytes or ovarian tissue should be discussed with women receiving endocrine therapy alone (5 – 10 years) to treat breast cancer.

Consensus-based Recommendation 2.R8

Expert consensus

Strength of consensus ++

The possibility of postponing or interrupting endocrine therapy may be discussed with the patient if this would allow her to have children early.


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4  Methods of Fertility Protection for Girls and Women

([Figs. 1] and [2])

Zoom Image
Fig. 1 Flow diagram of potential approaches to protect the fertility of girls and women after the onset of menarche before they start gonadotoxic therapy.
Zoom Image
Fig. 2 Fertility protection for women based on oncologic therapy and the available timeframe (modified from [1]).

4.1  Organ-preserving surgery

There are a number of S3 guidelines on the treatment of patients with malignant ovarian tumors, cervical cancer und endometrial cancer. To prevent discrepancies between guidelines, the guideline coordinators of the S3 guidelines and the coordinators of the S2k guideline on fertility preservation unanimously agreed to incorporate the relevant Statements, Recommendations and background texts from the S3 guidelines into the S2k guideline. The relevant Recommendations and Statements are available in the long version of the guideline.


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4.2  Ovariopexy and gonadal protection for radiotherapy

Consensus-based Statement 4.S25

Expert consensus

Strength of consensus +++

Transposition of the ovaries out of the area which will be irradiated may reduce the risk of radiogenic ovarian insufficiency.

Consensus-based Recommendation 4.R33

Expert consensus

Strength of consensus +++

The possibility of an ovariopexy to preserve ovarian function must be discussed before commencing radiotherapy/radiochemotherapy of the lesser pelvis.

Consensus-based Statement 4.S36

Expert consensus

Strength of consensus +++

If ovariopexy is performed, ovarian tissue may be harvested at the same time for cryopreservation.


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4.3  GnRH agonists

Consensus-based Statement 4.S47

Expert consensus

Strength of consensus ++

The data is still contradictory, so administering GnRH agonists as the only method for fertility protection is not sufficient.

Consensus-based Statement 4.S58

Expert consensus

Strength of consensus +++

Because of the contradictory study results, it is currently not possible to evaluate the benefit of administering a GnRH agonist.

Consensus-based Recommendation 4.R34

Expert consensus

Strength of consensus +++

Depending on the underlying tumor entity, GnRH agonists may be offered as a fertility protection measure if the patient has been informed in detail.


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4.4  Cryopreservation of fertilized or unfertilized oocytes

Consensus-based Statement 4.S19

Expert consensus

Strength of consensus +++

Cryopreservation of fertilized and unfertilized oocytes is an established technique in reproductive medicine which can be used before starting gonadotoxic therapy.

4.4.1  Controlled ovarian stimulation to harvest oocytes in cancer patients

Consensus-based Statement 4.S20

Expert consensus

Strength of consensus +++

A protocol with the lowest possible risk of ovarian hyperstimulation syndrome should be used for ovarian stimulation treatment to protect fertility.


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4.4.2  Cryopreservation of unfertilized oocytes

([Table 6])

Table 6 Outcomes for unfertilized oocytes after slow freezing or vitrification (modified from [8] and [9]).

Slow freezing

Vitrification

Survival rate per unfertilized oocyte after cryopreservation/thawing

45 – 67%

80 – 90%

Fertilization rate per unfertilized oocyte after cryopreservation/thawing

54 – 68%

76 – 83%

Clinical pregnancy rate/transfers

11.6%

44.9% (p = 0.002)

Congenital malformation rate

0.5%

1.3%

Consensus-based Statement 4.S21

Expert consensus

Strength of consensus ++

In contrast to the cryopreservation of fertilized oocytes, the cryopreservation of unfertilized oocytes is not associated with a significantly increased rate of malformations or developmental deficits in children.


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4.4.3  Cryopreservation of fertilized oocytes

([Tables 7] and [8])

Table 7 Survival rate and development of embryos after slow freezing or vitrification (open/closed) (modified from [10]).

Slow freezing

Vitrification (open/closed)

* p < 0,001

Survival rate per embryo after cryopreservation/thawing

63.8%

89.4%*/87.6%*

Rate of intact morphology of all blastomeres per embryo after cryopreservation/thawing

44.3%

80.1%*/76.1%*

Table 8 Pregnancy outcomes for blastocysts after slow freezing or vitrification (modified from [11] and [8]).

Slow freezing

Vitrification

* p = significant, ** ARR: 1.38, 95% CI: 1.32–1.45, *** ARR: 1.41, 95% CI: 1.34–1.49

Rate of transferred blastocysts per cryopreservation/thawing

71.4%

84.5%*

Rate of clinical pregnancies per transferred blastocyst

23.8%

32.7%**

Rate of live births per transferred blastocyst

17.7%

24.8%***

Consensus-based Recommendation 4.R35

Expert consensus

Strength of consensus +++

The cryopreservation of unfertilized oocytes must be additionally offered, even if the patient has a partner.


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4.5  Cryopreservation of ovarian tissue

Consensus-based Statement 4.S22

Expert consensus

Strength of consensus ++

Cryopreservation of ovarian tissue is an established method to restore fertility after receiving treatment for cancer.

Consensus-based Statement 4.S23

Expert consensus

Strength of consensus ++

Cryopreservation of ovarian tissue may be carried out at any time of the menstrual cycle and does not lead to any relevant delay in oncologic therapy.

4.5.1  Harvesting and transport of ovarian tissue

Consensus-based Recommendation 4.R36

Expert consensus

Strength of consensus +++

The harvested tissue must be cooled (4 – 8 °C) during its transportation to a center which specializes in cryopreservation. The harvested tissue must be processed promptly, at the very latest 24 hours after harvesting.


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4.5.2  Cryopreservation of harvested tissue

Slow freezing is currently recommended for the cryopreservation of ovarian tissue because of the higher efficacy of this method in routine clinical practice [12], [13], [14].


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4.5.3  Transplantation of tissue

Consensus-based Recommendation 4.R37

Expert consensus

Strength of consensus +++

Ovarian tissue must be transplanted orthotopically, i.e. on or into the ovary or close to the ovary in the retroperitoneal space.

Consensus-based Recommendation 4.R38

Expert consensus

Strength of consensus +++

The patientʼs fertility (tubal, uterine and extrauterine factors) must be assessed when transplanting ovarian tissue and, if possible, corrections must carried out where necessary.


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4.5.4  Risk of tumor or disease recurrence after retransplantation

([Table 9])

Table 9 Risk of ovarian metastasis for various tumor types (modified from Dolmans et al. [14] and Bastings et al. [15]).

High risk

Moderate risk

Low risk

  • leukemia

  • neuroblastoma

  • Burkittʼs lymphoma

  • ovarian tumors

  • stage IV breast cancer
    (lobular subtypes)

  • bowel cancer

  • endometrial carcinoma

  • gastric cancer

  • cervical adenocarcinoma

  • non-Hodgkinʼs lymphoma

  • Ewingʼs sarcoma

  • stage I – III breast cancer (ductal subtypes)

  • cervical squamous cell carcinoma

  • Hodgkinʼs lymphoma

  • osteosarcoma

  • non-genital rhabdomyosarcoma

  • Wilmsʼ tumor

Consensus-based Statement 4.S24

Expert consensus

Strength of consensus +++

The risk of ovarian metastasis cannot be excluded for any type of tumor. To date, an increased risk has been found for leukemia, neuroblastoma, Burkittʼs lymphoma and malignant ovarian tumors.

Consensus-based Recommendation 4.R39

Expert consensus

Strength of consensus +++

The patient must be informed before harvesting the tissue about the possible risk of transferring malignant cells by transplanting the harvested ovarian tissue.


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4.6  Fertility-preserving or fertility-creating/fertility-restoring methods following uterine radiotherapy

Consensus-based Recommendation 4.R40

Expert consensus

Strength of consensus ++

If the patient wishes to have children, the dose administered to the uterus must be kept as low as possible using the latest radiation planning and techniques.


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4.7  Combinations of fertility-protecting methods

Consensus-based Recommendation 4.R41

Expert consensus

Strength of consensus +++

The patient must be offered combinations of different fertility-preserving methods (e.g. cryopreservation of oocytes, cryopreservation of ovarian tissue and/or the administration of GnRH agonists) to improve the efficacy of fertility protection methods.


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6  Recommendations for Selected Tumor Entities in Women

6.1  Breast cancer

6.1.1  Fertility protection counseling for women with breast cancer

Consensus-based Recommendation 6.R3

Expert consensus

Strength of consensus ++

Every fertile woman with breast cancer who might wish to have children must receive counseling about ovarian toxicity and the available methods to protect fertility before starting any potentially gonadotoxic therapy.

Consensus-based Recommendation 6.R4

Expert consensus

Strength of consensus ++

Patients with metastatic breast cancer must receive individualized information on fertility protection which must also take account of the prognosis of a more limited life expectancy.


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6.1.2  Pregnancy after breast cancer

Consensus-based Statement 6.S36

Expert consensus

Strength of consensus ++

According to retrospective observational studies, pregnancy after treatment for breast cancer is not associated with a poorer prognosis with regard to the underlying disease.


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6.1.3  Limited fertility due to chemotherapy for breast cancer

The standard chemotherapy protocols to treat breast cancer in young women are anthracycline- and taxane-based chemotherapies. The rule of thumb for persistent amenorrhea following anthracycline-taxane-based regimens is estimated to be 10 – 20% for women aged < 30 years, while the rate of persistent amenorrhea for women aged more than 30 years ranges from 13 – 68%, depending on the patientʼs age [16], [17].


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6.1.4  Limited fertility due to radiotherapy

Consensus-based Statement 6.S32

Expert consensus

Strength of consensus +++

Regional radiotherapy to treat breast cancer is not associated with reduced fertility.


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6.1.5  Special aspects of fertility protection for women with hormone receptor-positive breast cancer, limited fertility due to endocrine therapy

Consensus-based Recommendation 6.R55

Expert consensus

Strength of consensus ++

If the patient has been carefully informed about the potential risks, pausing anti-tumor endocrine therapy (after a minimum of 2 years of therapy) may be considered to allow the patient to have children, after which the patient would resume therapy.


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6.1.6  Potential fertility protection methods for patients with breast cancer

([Table 10])

Table 10 Retrospective studies on methods of cryopreservation in women with breast cancer.

Authors

Study

Number of women

Methods

Country

Lawrenz et al., 2012 [18]

retrospective, single center

n = 56

ovarian tissue cryopreservation, GnRHa, hormone stimulation and cryopreservation of oocytes, combinations also possible

Germany

Turan et al., 2013 [19]

retrospective cohort study

single center

n = 78

hormone stimulation and cryopreservation of oocytes

USA

Sigismondi et al., 2015 [20]

retrospective, single center

n = 31

ovarian tissue cryopreservation, hormone stimulation and cryopreservation of oocytes

Italy

Takae et al., 2015 [21]

retrospective, single center

n = 27

combination of ovarian tissue cryopreservation and hormone stimulation with cryopreservation of oocytes

Japan

Dahhan et al., 2015 [22]

retrospective, single center

n = 16

hormone stimulation and cryopreservation of oocytes

Netherlands

Oktay et al., 2015 [23]

retrospective, single center

n = 131

hormone stimulation with/without letrozole and cryopreservation of oocytes

USA

Consensus-based Statement 6.S33

Expert consensus

Strength of consensus +++

Irrespective of the patientʼs hormone status, there are no conclusive data about the potential impact of hormone stimulation for oocyte retrieval before starting planned neoadjuvant systemic therapy for breast cancer on the patientʼs oncologic prognosis.

Consensus-based Recommendation 6.R56

Expert consensus

Strength of consensus ++

Hormone stimulation for oocyte retrieval can be done in patients with hormone receptor-positive breast cancer receiving concomitant anti-hormone treatment (e.g. aromatase inhibitors or tamoxifen).


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6.1.7  GnRH agonists (GnRHa) for women with breast cancer

A recent systematic meta-analysis about the use of GnRHa in women with breast cancer [26] evaluated the data from 1962 women, 541 of whom received chemotherapy without GnRHa and 521 of whom were treated with chemotherapy and GnRHa [26]. The rate of spontaneous menstruation recurrence after completing chemotherapy was higher in the group treated with concomitant GnRHa (OR: 2.57; 95% CI: 1.65 – 4.01; p < 0.0001). However, there was no significant difference in pregnancy rates between the two groups. Another recent meta-analysis (n = 1231, [27]) found a significantly reduced risk of premature ovarian insufficiency (OR: 0.36; 95% CI: 0.41 – 0.73, p < 0.001) for patients who received concomitant GnRHa during chemotherapy, together with a slightly but significantly increased pregnancy rate (OR: 1.83; 95% CI: 1.02 – 3.28; p = 0.041).


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6.1.8  Reduced ovarian reserve in women with BRCA1 mutation

Comparative studies have pointed out that women with BRCA1 mutation may have reduced ovarian reserve compared to healthy women [24], [25].


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6.2  Ovarian/borderline tumors

6.2.1  Borderline tumors

Consensus-based Recommendation 6.R57

Expert consensus

Strength of consensus +++

After women who have had fertility-preserving surgery to treat an ovarian/borderline tumor and who wish to have children have been informed about the potential risks involved, physicians may consider offering hormone stimulation to them as part of fertility treatment.

Consensus-based Recommendation 6.R58

Expert consensus

Strength of consensus +++

Before undergoing bilateral salpingo-oophorectomy, women should be offered the possibility of cryopreserving unfertilized and fertilized oocytes.

Consensus-based Recommendation 6.R59

Expert consensus

Strength of consensus +++

Cryopreservation of ovarian tissue may be considered.


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6.2.2  Ovarian cancer

Consensus-based Statement 6.S34

Expert consensus

Strength of consensus ++

Fertility treatment is possible in patients with early ovarian cancer (FIGO Ia, G1/G2) who were treated using a fertility-preserving approach and were given detailed information about the risks.


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6.3  Solid tumors

6.3.1  Sarcomas

Consensus-based Recommendation 6.R60

Expert consensus

Strength of consensus +++

Every fertile woman with sarcoma who may wish to have a child must be informed about the ovarian toxicity of treatment and the methods of preserving fertility before starting a potentially gonadotoxic therapy.

Consensus-based Statement 6.S35

Expert consensus

Strength of consensus ++

There are no indications that pregnancy after treatment for sarcoma will result in a poorer prognosis.

Consensus-based Statement 6.S36

Expert consensus

Strength of consensus ++

Depending on the patientʼs age, chemotherapy to treat osteosarcoma and soft tissue sarcoma will result in primary ovarian insufficiency.

Consensus-based Recommendation 6.R61

Expert consensus

Strength of consensus +++

Patients with sarcoma should be offered cryopreservation of ovarian tissue to protect fertility. The risk of recurrence caused by transplantation of the tissue cannot be excluded and must be discussed with the patient before harvesting ovarian tissue.

Consensus-based Recommendation 6.R62

Expert consensus

Strength of consensus +++

After the onset of puberty, patients with sarcoma should be informed about the possibility of cryopreserving oocytes, if the start of oncologic therapy can be postponed by at least 2 weeks.

Consensus-based Recommendation 6.R63

Expert consensus

Strength of consensus ++

A GnRH agonist can be administered to patients with sarcoma during gonadotoxic therapy.


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6.3.2  Colorectal cancer

Consensus-based Recommendation 6.R64

Expert consensus

Strength of consensus +++

Every fertile woman with colorectal cancer who may wish to have a child must be informed about the ovarian toxicity of treatment and methods of preserving fertility before starting a potentially gonadotoxic therapy.

Consensus-based Statement 6.S37

Expert consensus

Strength of consensus ++

According to case reports, pregnancy after rectal cancer is not associated with a poorer oncologic prognosis.

Consensus-based Statement 6.S38

Expert consensus

Strength of consensus ++

Chemotherapeutic treatment of colorectal cancer with 5-fluorouracil, folinic acid and oxaliplatin is reported to have a low risk of ovarian insufficiency.

Consensus-based Recommendation 6.R65

Expert consensus

Strength of consensus +++

Patients with colorectal cancer should be offered cryopreservation of ovarian tissue to protect fertility. The risk of disease recurrence caused by transplantation cannot be excluded and must be discussed with the patient before harvesting ovarian tissue.

Consensus-based Recommendation 6.R66

Expert consensus

Strength of consensus +++

After the onset of puberty, patients with colorectal cancer should be informed about the possibility of cryopreserving oocytes if the start of oncologic therapy can be postponed by at least 2 weeks.

Consensus-based Recommendation 6.R67

Expert consensus

Strength of consensus ++

A GnRH agonist can be administered to patients with colorectal cancer during gonadotoxic therapy.


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6.4  Hematologic disease

6.4.1  Lymphomas (Hodgkinʼs and non-Hodgkinʼs lymphoma)

Consensus-based Statement 6.S39

Expert consensus

Strength of consensus +++

With lymphomas, the risk of primary ovarian insufficiency depends on the chemotherapy protocol used.

Consensus-based Recommendation 6.R68

Expert consensus

Strength of consensus +++

Cryopreservation of ovarian tissue to protect fertility must be offered to patients with lymphoma who are expected to have a high risk of premature ovarian insufficiency from oncologic therapy. The risk of ovarian metastasis is low for Hodgkinʼs lymphoma and high for non-Hodgkinʼs lymphoma and Burkittʼs lymphoma.

Consensus-based Recommendation 6.R69

Expert consensus

Strength of consensus +++

After the onset of puberty, patients with lymphoma should be informed about the possibility of cryopreserving oocytes if the start of oncologic therapy can be postponed by at least 2 weeks.

Consensus-based Recommendation 6.R70

Expert consensus

Strength of consensus +++

A GnRH agonist can be administered to patients with lymphoma during gonadotoxic therapy. This can help prevent thrombocytopenic menorrhagia.


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6.4.2  Leukemia

6.4.2.1  Acute lymphatic leukemia (ALL)

Consensus-based Statement 6.S40

Expert consensus

Strength of consensus +++

The risk of infertility after treatment for ALL depends on the protocol used for treatment. Women who were treated with a conditioning protocol to prepare them for stem cell transplantation have a high risk of infertility. Patients treated with a conventional protocol have a low risk of infertility.

Consensus-based Statement 6.S41

Expert consensus

Strength of consensus +++

Depending on the dose, cranial irradiation during treatment for ALL can lead to treatable impairment of the hypothalamic-hypophyseal axis.

Consensus-based Recommendation 6.R71

Expert consensus

Strength of consensus ++

Patients with ALL who have a high risk of POI from therapy and who cannot postpone their gonadotoxic therapy can be offered the option of cryopreserving ovarian tissue to protect their fertility.

Consensus-based Recommendation 6.R72

Expert consensus

Strength of consensus +++

The risk of tumor recurrence after autotransplantation of ovarian tissue is considered to be high in patients with ALL, and autotransplantation is therefore not recommended.

Consensus-based Recommendation 6.R73

Expert consensus

Strength of consensus ++

After the onset of puberty, patients with ALL should be informed about the possibility of cryopreserving oocytes if the start of oncologic therapy can be postponed by at least 2 weeks.

Consensus-based Recommendation 6.R74

Expert consensus

Strength of consensus +++

A GnRH agonist can be administered to patients with ALL during gonadotoxic therapy. This can help prevent thrombocytopenic menorrhagia.


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6.4.2.2  Acute myeloid leukemia (AML)

Consensus-based Statement 6.S42

Expert consensus

Strength of consensus +++

The risk of infertility after treatment for AML depends on the protocol used for treatment. Women treated with a conditioning protocol to prepare them for stem cell transplantation have a high risk of infertility. Patients treated with a conventional protocol have a low risk of infertility.

Consensus-based Recommendation 6.R75

Expert consensus

Strength of consensus +++

Patients with AML who have a high risk of POI from therapy and who cannot postpone their gonadotoxic therapy can be offered the option of cryopreserving ovarian tissue to protect their fertility.

Consensus-based Recommendation 6.R76

Expert consensus

Strength of consensus +++

The risk of tumor recurrence after autotransplantation of ovarian tissue is considered to be high in patients with AML, and autotransplantation is therefore not recommended.

Consensus-based Recommendation 6.R77

Expert consensus

Strength of consensus +++

After the onset of puberty, patients with AML should be informed about the possibility of cryopreserving oocytes if the start of oncologic therapy can be postponed by at least 2 weeks.

Consensus-based Recommendation 6.R78

Expert consensus

Strength of consensus +++

A GnRH agonist can be administered to patients with AML during gonadotoxic therapy. This can help prevent thrombocytopenic menorrhagia.


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6.4.2.3  Chronic myelogenous leukemia (CML)

Consensus-based Statement 6.S43

Expert consensus

Strength of consensus +++

The risk of ovarian insufficiency following the administration of tyrosine kinase inhibitors (TKI) is unclear, with TKI reported to have a teratogenic potential.

Consensus-based Recommendation 6.R79

Expert consensus

Strength of consensus +++

The risk of disease recurrence after autotransplantation of ovarian tissue is considered to be high in patients with CML, and autotransplantation is therefore not recommended.


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6.4.2.4  Stem cell transplantation

Consensus-based Recommendation 6.R80

Expert consensus

Strength of consensus +++

Women treated with a conditioning protocol to prepare them for stem cell transplantation have a high risk of infertility. These patients must be informed and receive counseling about methods to protect their fertility.

Consensus-based Recommendation 6.R81

Expert consensus

Strength of consensus ++

After the onset of puberty and before starting conditioning for stem cell transplantation, patients should be informed about the possibility of cryopreserving oocytes if the start of oncologic therapy can be postponed by at least 2 weeks.

Consensus-based Recommendation 6.R82

Expert consensus

Strength of consensus +++

Patients can be offered the option of cryopreserving ovarian tissue to protect fertility before undergoing stem cell transplantation.


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8  Malignant Disease in Children and Adolescents

In addition to the established methods to protect fertility before and after treatment for malignant disease mainly targeting post-pubertal boys and girls, experimental methods are also available, particularly for prepubertal children. Listed below are instructions concerning the use of fertility protection methods which need to be taken into account before starting therapy.

Consensus-based Recommendation 8.R92

Expert consensus

Strength of consensus +++

The efficacy of administering drugs for fertility protection (e.g. a GnRH agonist) in childhood or early adolescence is still questionable. GnRH agonists must not be administered to prepubertal patients.

Consensus-based Recommendation 8.R93

Expert consensus

Strength of consensus +++

Depending on the expected radiation dose administered to the ovary, the possibility of ovariopexy must be discussed during the tumor conference. The recommendation for ovariopexy must be discussed with the patient and her family.

Consensus-based Recommendation 8.R94

Expert consensus

Strength of consensus +++

After puberty patients can undergo stimulation treatment to cryopreserve oocytes. This must be done before starting treatment for malignant disease if cancer therapy can be postponed by 2 weeks.

Consensus-based Recommendation 8.R95

Expert consensus

Strength of consensus +++

It is currently not clear what the indications for cryopreserving ovarian tissue from prepubertal and peripubertal girls are. The decision for or against cryopreservation requires the type of therapy and the gonadotoxic dose to be weighed up in each individual case.

Consensus-based Recommendation 8.R96

Expert consensus

Strength of consensus +++

After puberty, potential options for fertility preservation include cryopreserving sperm (ejaculation, electrostimulation, testicular biopsy with testicular sperm extraction [TESE]) and cryopreserving testicular tissue as a fertility reserve for assisted reproduction techniques to be used at a later date. The patient and his family must be informed about these options.

Consensus-based Statement 8.S48

Expert consensus

Strength of consensus +++

The cryopreservation of immature testicular tissue extracted by biopsy before the onset of puberty is still in its experimental stages. The subsequent maturation of sperm from spermatogonial stem cells, which would be necessary for this approach, is currently not yet possible in humans. Transplanting cryopreserved tissue always carries the risk of transplanting malignant cells.


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9  Psychological and Ethical Aspects of Fertility Preservation

Consensus-based Statement 9.S49

Expert consensus

Strength of consensus +++

All patients of reproductive age with malignant disease and children with malignant disease and their parents should be offered counseling and advice on fertility protection using a biopsychosocial framework. Information about the options for and the limits of fertility protection should be made available to affected patients both orally and in writing (e.g., in the form of publications like “Die Blauen Ratgeber” – a German series of publications issued by the German Cancer Society) through low-threshold publications which enable patients to make their decisions based on informed consent.

Consensus-based Statement 9.S50

Expert consensus

Strength of consensus +++

During open-ended counseling, the different options and perspectives available must be presented and discussed without bias or preference: oncologic therapy without fertility protection, oncologic therapy after fertility protection measures, and pregnancy, childbirth and starting a family must be discussed in ways that take account of different healing processes and courses of disease.


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Appendix to the Guideline

A standard operating procedure (SOP) on managing the contact with a patient before the patient starts oncologic treatment which will reduce their fertility while the patient may still want to have children is included in the appendix of the long (German) version of the guideline, together with leaflets on preserving fertility which were compiled together with the German Cancer Society (DKG).


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Guideline Program

Editors

Leading Professional Medical Associations

Zoom Image

German Society of Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e. V. [DGGG])
Head Office of DGGG and Professional Societies
Hausvogteiplatz 12, DE-10117 Berlin
[email protected]
http://www.dggg.de/


President of DGGG
Prof. Dr. Birgit Seelbach-Göbel
Universität Regensburg
Klinik für Geburtshilfe und Frauenheilkunde
St. Hedwig-Krankenhaus Barmherzige Brüder
Steinmetzstraße 1–3, DE-93049 Regensburg


DGGG Guidelines Representative
Prof. Dr. med. Matthias W. Beckmann
Universitätsklinikum Erlangen, Frauenklinik
Universitätsstraße 21–23, DE-91054 Erlangen


Prof. Dr. med. Erich-Franz Solomayer
Universitätsklinikum des Saarlandes
Geburtshilfe und Reproduktionsmedizin
Kirrberger Straße, Gebäude 9, DE-66421 Homburg


Guidelines Coordination
Dr. med. Paul Gaß, Christina Fuchs, Marion Gebhardt
Universitätsklinikum Erlangen
Frauenklinik
Universitätsstraße 21–23
DE-91054 Erlangen
[email protected]
http://www.dggg.de/leitlinienstellungnahmen

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Austrian Society of Gynecology and Obstetrics (Österreichische Gesellschaft für Gynäkologie und Geburtshilfe [OEGGG])
Innrain 66A, AT-6020 Innsbruck
[email protected]
http://www.oeggg.at


President of OEGGG
Prof. Dr. med. Petra Kohlberger
Universitätsklinik für Frauenheilkunde Wien
Währinger Gürtel 18–20, AT-1180 Wien


OEGGG Guidelines Representative
Prof. Dr. med. Karl Tamussino
Universitätsklinik für Frauenheilkunde und Geburtshilfe Graz
Auenbruggerplatz 14
AT-8036 Graz


Prof. Dr. med. Hanns Helmer
Universitätsklinik für Frauenheilkunde Wien
Währinger Gürtel 18–20, AT-1090 Wien

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Swiss Society of Gynecology and Obstetrics (Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe [SGGG])
Gynécologie Suisse SGGG
Altenbergstraße 29, Postfach 6, CH-3000 Bern 8
[email protected]
http://www.sggg.ch/


President of SGGG
Dr. med. David Ehm
FMH für Geburtshilfe und Gynäkologie
Nägeligasse 13
CH-3011 Bern


SGGG Guidelines Representative
Prof. Dr. med. Daniel Surbek
Universitätsklinik für Frauenheilkunde
Geburtshilfe und feto-maternale Medizin
Inselspital Bern
Effingerstraße 102
CH-3010 Bern


Prof. Dr. med. René Hornung
Kantonsspital St. Gallen, Frauenklinik
Rorschacher Straße 95, CH-9007 St. Gallen


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Correspondence/Korrespondenzadresse

Prof. Dr. rer. nat. Ralf Dittrich
Frauenklinik
Universitätsklinikum Erlangen
Universitätsstraße 21 – 23
91054 Erlangen


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Fig. 1 Flow diagram of potential approaches to protect the fertility of girls and women after the onset of menarche before they start gonadotoxic therapy.
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Fig. 2 Fertility protection for women based on oncologic therapy and the available timeframe (modified from [1]).
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Abb. 1 Flussdiagramm zum allgemeinen Vorgehen bei Fertilitätserhaltung vor einer gonadotoxischen Therapie bei postmenarchalen Mädchen und Frauen.
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Abb. 2 Fertilitätsprotektive Maßnahmen für Frauen in Abhängigkeit von der onkologischen Therapie und dem verfügbaren Zeitfenster (modifiziert nach [1]).
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