Dirigente medico

Centro Sterilità P. Bertocchi

S.O.C. Ostetricia e Ginecologia, Dipartimento Ostetrico, Ginecologico e Pediatrico

A.O. Arcispedale S.Maria Nuova, Reggio Emilia

MT  Villani  

Progetto per la preservazione della fertilità femminile a Reggio Emilia

45%  

37%    

RODRIGUEZ-­‐WALLBERG,  2014  

La  sopravvivenza  a  5  anni  dalla  diagnosi  ha  raggiunto  

complessivamente  il  78%  per  i  tumori  in  eta'  pediatrica  e  l'82%  per  i  tumori  dell'adolescente  

Efficacia Possibile sterilita’

L’effeOo  gonadotossico  di  alcuni  traOamenP    

chemio-­‐radioterapici  è  oggi  comprovato.    

© 2014 Rodriguez-Wallberg and Oktay. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further

permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Cancer Management and Research 2014:6 105–117

Cancer Management and Research Dovepress

submit your manuscript | www.dovepress.com

Dovepress 105

R E V I E W

open access to scientific and medical research

Open Access Full Text Article

http://dx.doi.org/10.2147/CMAR.S32380

Fertility preservation during cancer treatment: clinical guidelines

Kenny A Rodriguez-Wallberg1,2

Kutluk Oktay3,4

1Karolinska Institutet, Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, 2Reproductive Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; 3Innovation Institute for Fertility Preservation, Rye and New York, 4Department of Obstetrics and Gynecology, New York Medical College, Valhalla, NY, USA

Correspondence: Kenny A Rodriguez-Wallberg Reproductive Medicine, Karolinska University Hospital Huddinge, Novumhuset Plan 4, SE-141 86 Stockholm, Sweden Email kenny.rodriguez-wallberg@karolinska.se Kutluk Oktay Innovation Institute for Fertility Preservation, 139 E 23rd St, New York, NY 10010, USA Email koktay@fertilitypreservation.org

Abstract: The majority of children, adolescents, and young adults diagnosed with cancer today will become long-term survivors. The threat to fertility that cancer treatments pose to young patients cannot be prevented in many cases, and thus research into methods for fertility preservation is developing, aiming at offering cancer patients the ability to have biologically related children in the future. This paper discusses the current status of fertility preservation methods when infertil-ity risks are related to surgical oncologic treatments, radiation therapy, or chemotherapy. Several scientific groups and societies have developed consensus documents and guidelines for fertility preservation. Decisions about fertility and imminent potentially gonadotoxic therapies must be made rapidly. Timely and complete information on the impact of cancer treatment on fertility and fertility preservation options should be presented to all patients when a cancer treatment is planned.Keywords: fertility preservation, cancer, cryopreservation, ovarian tissue transplantation, fertility-sparing surgery, cancer survival, quality of life

IntroductionThe number of reported new cancer cases is increasing every year. In the Swedish Cancer Registry, the validity of which relies on the inclusion of approximately 98% of cases having morphologic verification, the average annual increase has been 2.1% for men and 1.5% for women during the last two decades.1 Only about half of this increase is explained by aging of the population and in many cases cancer patients are very young. Similar data have been observed in other European countries and in the US.2 The good news is that the probability of surviving cancer today is high and is continually improving. Rates of survival today are above 80% for various cancer types, in particular for very young patients, such as those presenting with cancer in childhood or early adulthood.3 Survivorship issues have therefore become highly relevant as well as quality of survival encompassing all health aspects.

The diagnosis of cancer at a young age, when individuals may have not yet started their families, poses unique challenges because treatments for cancer may induce ovar-ian or testicular failure by damaging ovarian follicles in females and spermatogonia in the testis in males. Gonadal failure may affect all aspects of reproductive health, including pubertal development, hormone production, and sexual function in adults. When cancer is treated by surgery, fertility may be impaired by removal or damage of the organs needed for reproduction.

The gonadotoxic effects of chemotherapy and radiation therapy are well recognized. These are dose-dependent and have been well characterized regarding the protocols used.3–12 Radiotherapy in females may also damage the uterus.13,14 Gonadotoxicity is

© 2014 Rodriguez-Wallberg and Oktay. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further

permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Cancer Management and Research 2014:6 105–117

Cancer Management and Research Dovepress

submit your manuscript | www.dovepress.com

Dovepress 105

R E V I E W

open access to scientific and medical research

Open Access Full Text Article

http://dx.doi.org/10.2147/CMAR.S32380

Fertility preservation during cancer treatment: clinical guidelines

Kenny A Rodriguez-Wallberg1,2

Kutluk Oktay3,4

1Karolinska Institutet, Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, 2Reproductive Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; 3Innovation Institute for Fertility Preservation, Rye and New York, 4Department of Obstetrics and Gynecology, New York Medical College, Valhalla, NY, USA

Correspondence: Kenny A Rodriguez-Wallberg Reproductive Medicine, Karolinska University Hospital Huddinge, Novumhuset Plan 4, SE-141 86 Stockholm, Sweden Email kenny.rodriguez-wallberg@karolinska.se Kutluk Oktay Innovation Institute for Fertility Preservation, 139 E 23rd St, New York, NY 10010, USA Email koktay@fertilitypreservation.org

Abstract: The majority of children, adolescents, and young adults diagnosed with cancer today will become long-term survivors. The threat to fertility that cancer treatments pose to young patients cannot be prevented in many cases, and thus research into methods for fertility preservation is developing, aiming at offering cancer patients the ability to have biologically related children in the future. This paper discusses the current status of fertility preservation methods when infertil-ity risks are related to surgical oncologic treatments, radiation therapy, or chemotherapy. Several scientific groups and societies have developed consensus documents and guidelines for fertility preservation. Decisions about fertility and imminent potentially gonadotoxic therapies must be made rapidly. Timely and complete information on the impact of cancer treatment on fertility and fertility preservation options should be presented to all patients when a cancer treatment is planned.Keywords: fertility preservation, cancer, cryopreservation, ovarian tissue transplantation, fertility-sparing surgery, cancer survival, quality of life

IntroductionThe number of reported new cancer cases is increasing every year. In the Swedish Cancer Registry, the validity of which relies on the inclusion of approximately 98% of cases having morphologic verification, the average annual increase has been 2.1% for men and 1.5% for women during the last two decades.1 Only about half of this increase is explained by aging of the population and in many cases cancer patients are very young. Similar data have been observed in other European countries and in the US.2 The good news is that the probability of surviving cancer today is high and is continually improving. Rates of survival today are above 80% for various cancer types, in particular for very young patients, such as those presenting with cancer in childhood or early adulthood.3 Survivorship issues have therefore become highly relevant as well as quality of survival encompassing all health aspects.

The diagnosis of cancer at a young age, when individuals may have not yet started their families, poses unique challenges because treatments for cancer may induce ovar-ian or testicular failure by damaging ovarian follicles in females and spermatogonia in the testis in males. Gonadal failure may affect all aspects of reproductive health, including pubertal development, hormone production, and sexual function in adults. When cancer is treated by surgery, fertility may be impaired by removal or damage of the organs needed for reproduction.

The gonadotoxic effects of chemotherapy and radiation therapy are well recognized. These are dose-dependent and have been well characterized regarding the protocols used.3–12 Radiotherapy in females may also damage the uterus.13,14 Gonadotoxicity is

ü  Nonostante l’evidenza che la perdita della fertilità nei pazienti sopravvissuti a un cancro sia correlata a distress psicologico e peggiori la qualità di vita, molti pazienti oncologici in età riproduttiva non ricevono adeguate informazioni o

non vengono inviati a specialisti per la preservazione della fertilità

ü  Questo contrasta con i dati che indicano che circa 3 pazienti oncologici su 4 con età inferiore a 35 anni e senza figli, al momento della terapia per il cancro

sarebbero interessati ad avere un figlio nella loro vita.

La  richiesta  di  preservazione  della  ferPlità  da  parte  dei  pazienP  è  in  

aumento  (5%  nel  2006  vs  15%  nel  2012).  

RUDDY,  2014;  LAMBERTINI,  2016  

TuOavia,  esiste  una  discrepanza  nella  preservazione  della  ferPlità    

in  base  al  sesso.  

L’età media della prima gravidanza nei paesi industrializzati è in costante aumento,

tra il 2006 e il 2010 la percentuale di donne >40 anni che ha avuto la prima gravidanza era circa il 20%

L’incidenza dei tumori prima di aver completato la

propria vita riproduttiva tende ad aumentare

Il Cancer Statistics ha riportato che circa il 10% dei casi di tumori femminili interessano donne <40 anni

Le evidenze scientifiche dimostrano che

una gravidanza dopo una neoplasia non peggiora la prognosi

Come  indicato  da  linee  guida  nazionali  ed  internazionali,  la  futura  

genitorialità  deve  essere  parte  integrante  del  percorso  diagnosPco-­‐

terapeuPco  del  paziente  oncologico  in  età  ferPle.  

LAMBERTINI,  2016;  FRYDMAN,  2016  American  Society  for  ReproducPve  Medicine,  2013  

 

 

American  Society  of  Clinical  Oncology,  2013  

Associazione  Italiana  di  Oncologia  Medica,  2013  

European  Society  for  Medical  Oncology,  2013  

ONCOFERTILITA’/PRESERVAZIONE DELLA FERTILITA’

1936 1938 1945 1949 1953 1962 1983 1985 1986 1987 1990 1992 1996 1776 1999

2003 2013

PRIME OSSERVAZIONI

SUL CONGELAMENTO

CELLULARE (SPALLANZANI)

SOPRAVVIVENZA DI SPERMATOZOI

ANIMALI CONGELATI IN ELIO A -296,5°C

(JAHNEL)

SOPRAVVIVENZA DEGLI

SPERMATOZOI MANTENUTI A

BASSE TEMPERATURE

(-160°C)

GLICEROLO COME

CRIOPROTETTORE PER GLI

SPERMATOZOI (POLGE)

GRAVIDANZA DA

SPERMATOZOI CONGELATI

(BUNGE & SHERMAN)

PRIMA BANCA DEL SEME

GRAVIDANZA DA

EMBRIONI CONGELATI

(TROUNSON)

PROH COME CRIOPROTETTORE

EMBRIONARIO (LASSALLE)

PARTO DA

OVOCITI CONGELATI

(CHEN)

PARZIALE VALIDAZIONE

DELLA VITRIFICAZIONE

OVOCITARIA (ASRM)

CONGELAMENTO ULTRARAPIDO EMBRIONARIO (TROUNSON)

PARTO DA

EMBRIONI VITRIFICATI (GOROTS)

GRAVIDANZA DA

SPERMATOZOI TESTICOLARI CONGELATI (GIL-SALOM)

ICSI (PALERMO)

La  chiave  di  svolta  nella  diffusione  della  preservazione  della  ferPlità  è  stato  

il  progressivo  miglioramento  delle  procedure  di  crioconservazione.      

PARTI DA

OVOCITI VITRIFICATI

(KULESHOVA, YOON)

Studio multicentrico osservazionale.

Centro Coordinatore: Azienda Ospedaliera Universitaria San Martino di Genova – IRCCS – Istituto Nazionale per la Ricerca sul Cancro

Ente proponente: Assessorato alla Salute - Regione Liguria

Studio osservazionale di coorte prospettico sulla preservazione della fertilità nelle pazienti

giovani con patologia oncologica. PREFER (PREgnancy and FERtility).

Durata dello studio: 24 mesi (2012-2014)

Centri coinvolti

Obiettivi

Piano di valutazione

Piano di valutazione

Intervento proposto

Intervento proposto: Counselling riproduttivo con proposta di

protocolli gestionali di preservazione della fertilità.

Fruibilità della ricerca

Conoscenza circa le preferenze e le scelte delle giovani pazienti oncologiche.

Aumentare la consapevolezza degli addetti ai lavori circa

l’importanza del (corretto) counselling.

Indirizzare verso la strategia con il miglio rapporto rischio/beneficio.

Traslabilità della ricerca Realizzazione di un sistema clinico strutturato di tipologia “Hub and

Spoke”, allocando le attività in diverse tipologie di strutture del Sistema Sanitario Italiano (Aziende Ospedaliere, IRCCS pubblici e Privati, Istituti Oncologici, Università) dove in questi anni siano già state

compiute sperimentazioni di pratiche e procedure per la conservazione della fertilità.

Le strutture del progetto (HUBS) devono stabilire rapporti funzionali con altra tipologia di strutture (SPOKES), quali, ad esempio, Aziende

sanitarie territoriali o Unità operative oncologiche, chirurgiche, urologiche e pediatriche impossibilitate a realizzare progetti autonomi.

Sarà inoltre compito dell’attività progettuale stabilire un sistema, sotto forma di rete tra le HUBS per la condivisione di protocolli, linee guida, dati, la creazione di un unico database da collegare ai Registri tumori

locali e nazionali per migliorare la rilevazione dei dati dello stato di salute dei pazienti lungo-sopravviventi.

Monitoraggio a cura del Centro Promotore.

I dati raccolti presso il Centro Clinical Trials dell’IRCCS AOU San Martino - IST

Monitoraggio dello studio

N° CONSULENZE: 50