Defining the whole of reproductive health in adolescent and young adult cancer populations: fertility is only one piece of the puzzle

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1 Guidelies Perspective Defiig the whole of reproductive health i adolescet ad youg adult cacer populatios: fertility is oly oe piece of the puzzle Gwedoly P Qui*1,2, Devi Murphy3, Ivaa Sehovic2 & Kelly Sawczy4 Practice Poits The adolescet ad youg adults (AYA) group (ages years) i ocology is ofte called the orpha cohort, as they have bee uderstudied for a variety of reasos. AYA populatios are i the distict situatio of dealig with a life-threateig illess alogside maagig major developmetal, persoal, educatioal ad occupatioal milestoes. This review highlights Natioal Comprehesive Cacer Network ad America Academy of Pediatrics guidelies o issues withi reproductive health, the ifluece of these guidelies i cliical practice ad the impact of missig pieces of the reproductive health puzzle for AYAs. Largely, these orgaizatios have ot itegrated the broad defiitios of reproductive health ito curret policies, which leaves sigificat gaps i medical ad ethical stadards of care. The Natioal Comprehesive Cacer Network AYA ocology guidelies offer a more comprehesive approach to care ad itegrate the UN Populatios Fud s refied reproductive health defiitio more successfully tha the America Academy of Pediatrics. A multidiscipliary approach is ecessary to bridge the gaps amog physicia practice guidelies. Uiversity of South Florida, College of Medicie, Departmet of Ocologic Sciece, Tampa, FL, USA Moffitt Cacer Ceter, Cacer Prevetio & Cotrol, Health Outcomes & Behavior Program, Tampa, FL, USA 3 Joatha Jaques Childre's Cacer Ceter, Miller Childre's Hospital, Log Beach, CA USA 4 All Childre s Hospital, Johs Hopkis Medicie, St Petersburg, FL, USA *Author for correspodece: gwe.qui@moffitt.org /CPR Future Medicie Ltd Cli. Pract. (2013) 10(3), part of ISSN

2 Guidelies Perspective Qui, Murphy, Sehovic & Sawczy Quality of life is a importat but distict issue for adolescet ad youg adults (AYA) compared with older adults. Reproductive health is a key aspect of health-related quality of life ad spas across physiological ad psychological domais. While fertility issues have had more attetio i the past 5 years, there are other aspects of reproductive health requirig recogitio by healthcare practitioers i AYA ocology. These iclude attetio to huma papillomavirus ad sexually trasmitted ifectio risk, cotraceptio ad sexual health i relatio to late effects of cacer ad treatmet. Alkylatig agets i chemotherapy, total-body radiatio or exteral-beam radiatio i a field that icludes the ovaries, testes or edocrie system may cause log-term impairmet to reproductive health fuctioig. We examie reproductive health i relatio to Natioal Comprehesive Cacer Network ad America Academy of Pediatrics guidelies for AYA cacer survivors i the USA. While fertility preservatio ad issues related to fertility are preset i the guidelies, cotraceptio, huma papillomavirus vaccie or other sexual health issues are icomplete. summary Recetly, the cliical commuity has ackowledged that adolescets ad youg adults (AYA) have uique eeds i cacer survivorship that require attetio separate from childre ad older adults, particularly as it relates to qualityof-life issues. While health-related quality of life does ot have a uiversal defiitio, it is typically defied as a broad dimesioal cocept icludig self reported measures of physical ad metal health [101]. I the USA, more tha 69,000 AYAs are diagosed with cacer each year [102]. The AYA populatio is comprised of people aged years; a age group that has ot see a improvemet i survival rates compared with those youger tha 15 years ad older tha 39 years of age [1]. The AYA group i ocology is ofte called the orpha cohort as they have bee uderstudied for a variety of reasos, primarily the difficulty o the part of researchers ad the populatio i creatig protocols ad methods that facilitate logitudial ad follow-up studies [2,3]. Furthermore, the biologic differeces betwee types of childhood ad AYA cacers were also left uatteded to util the early 2000s [4]. AYA populatios are i the distict situatio of dealig with a life-threateig illess alogside maagig major developmetal, persoal, educatioal ad occupatioal milestoes. Therefore, i additio to havig physiological ad biological health issues that exted beyod routie medical care, AYAs may experiece psychosocial issues such as eurocogitive problems from treatmet, difficulty becomig idepedet, reduced social skills, difficulty establishig relatioships, 302 Cli. Pract. (2013) 10(3) risk-takig behavior, body image dissatisfactio, sexual dysfuctio, loss of fertility ad reduced quality of life [5]. However, AYA cacer survivors are also kow to have higher health literacy ad adjustmet patters tha those who did ot experiece cacer [5,6]. Psychosocial issues should be moitored throughout survivorship care ad plaig. A area that compouds psychosocial late effects for AYAs is reproductive health. While specific attetio has bee paid to issues of fertility, this is oly oe piece of the reproductive health puzzle. I ocology settigs, fertility has gaied mometum as a importat quality-of-life issue; however it should ot mire the broader cotext of reproductive health that also impacts o AYA patiets. The WHO defies reproductive health as a state of complete physical, metal ad social wellbeig, ad ot merely the absece of disease or ifirmity, reproductive health addresses the reproductive processes, fuctios ad system at all stages of life [103]. Reproductive health, therefore, implies that people have the autoomy to choose resposible, satisfyig ad safe sexual behaviors, which may or may ot lead to reproductio. Idividuals have the right to decide if, whe ad how ofte to perform such acts [101]. This defiitio was expaded ad ameded i 2011 by the UN Populatios Fud (UNPF). The refied defiitio offers specific aspects of reproductive health that iclude the followig domais: family plaig; ateatal ad post-atal care; prevetio ad treatmet of ifertility; treatmet of reproductive

3 Reproductive health i adolescet & youg adult cacer populatios tract ifectios; prevetio, care ad treatmet of sexually trasmitted ifectios (STIs) ad HIV/AIDS; provisio of educatio o huma sexuality ad reproductive health; ad referrals for further diagosis ad maagemet of the above [104]. Numerous research efforts over the past two decades motivated the UNPF to expad the defiitio of reproductive health to capture relevat issues facig me ad wome. While this expasio of reproductive health i the iteratioal commuity is of great sigificace, it has yet to reach may policies o atioal ad state levels i the USA. The Natioal Comprehesive Cacer Network (NCCN) ad the America Academy of Pediatrics (AAP) are leaders i pediatric policies ad guidelies, ad serve as trusted sources for AYA ocologists throughout the USA to uphold medical ad ethical stadards, icludig stadards of care. The AYA defiitio is relatively ew ad patiets withi this populatio may be treated i pediatric or adult protocols or a combiatio. Thus, we look to the orgaizatios that gover both age groups to establish ad moitor stadards of care. The research questio examied was to idetify whether these orgaizatios had itegrated the revised reproductive health defiitio from the UNPF ito existig policy documets for AYA cacer patiets to esure comprehesive care. I this article, we highlight the NCCN ad AAP guidelies o issues withi reproductive health, the ifluece of these guidelies i cliical practice ad the impact of missig pieces of the reproductive health puzzle for AYAs. We chose to focus o the NCCN guidelies specifically because the NCCN Cliical Practice Guidelies are the most widely followed i 115 coutries, ad cover 97% of cacers [7]. Additioally, we chose to focus o the AAP guidelies due to the log-stadig ifluece o stadard-of-care practices i pediatrics throughout the USA. Aalysis of other, less atteded to guidelies, may have produced homogeous results ad had a ieffectual impact o cliical practice patters. Table 1 displays the iclusio or exclusio of ewly defied reproductive health issues withi the NCCN ad AAP guidelies specific to AYA cacer patiets. Largely, these orgaizatios have ot itegrated the broad defiitios of reproductive health ito curret policies, which leaves sigificat gaps i legal ad ethical stadards of care. Guidelies Perspective Family plaig Cotraceptio The NCCN advocates cotraceptio i its AYA cliical practice guidelies [105]. However, the recommedatio is isolated to the sectio regardig fertility cosideratios, ad offers oral cotraceptives oly as a method to suppress meses. The NCCN does ot address ay cotraidicatios of some cotraceptives, or strategies i the evet that emergecy cotraceptives are desired. The AAP provides professioal guidelies detailig the resposibility of health professioals to discuss cotraceptio with AYAs i the geeral populatio. There are details regardig the protectio agaist some cacers with oral cotraceptives, however, this is the oly referece to cacer i AAP s policy statemet o cotraceptio [8]. There is also o referece to cotraceptio for ocology patiets i AAP s log-term follow-up guidelies [9]. The AAP does have a policy statemet that addresses sexuality, cotraceptio ad the media, which explicitly recommeds agaist abstiece-oly educatio [10]. AYAs with cacer have uique cotraceptio eeds that require persoalized discussios with the healthcare team. Miscoceptios regardig the sexuality of AYA cacer patiets may ihibit discussios of cotraceptive use for this populatio, but research idicates that adolescets with cacer are at least as sexually active as their healthy couterparts [11]. Persoalized discussios regardig cotraceptio are warrated, as some types ca have iteractios with cacer treatmets. May pharmaceutical compaies have disclaimers o the websites of specific chemo therapy drugs that may produce cocomitat issues with a chose cotraceptive. For example, certai chemotherapies have bee show to decrease boe desity due to atimetabolites, such as methotrexate, i cojuctio with corticosteroids [12] ; therefore, female ijectable cotraceptives, which may also decrease boe desity [13], should be discouraged. There are also potetially harmful iteractios betwee hormoal cotraceptive itervetios ad estroge receptive tumors. For example, the progosis of wome with curret or recet breast cacer may worse with combied (cotaiig estroge ad progesti) cotraceptive use as breast cacer ca be a hormoally sesitive tumor [103,106]. I additio, the Society of Family Plaig has recommeded that wome of childbearig age udergoig cacer treatmet, such as chemotherapy ad tamoxife, 303

4 Guidelies Perspective Qui, Murphy, Sehovic & Sawczy Table 1. Guidelies for adolescet ad youg adult ocology. Subject Family plaig AAP NCCN AYA patiets should be maaged by a multidiscipliary team of Cotraceptio providers with expertise i cacer treatmet ad maagemet of family plaig, pregacy... (page MS-4) Mestrual suppressio (for fertility preservatio): oral cotraceptives may be used i protocols that are predicted to cause prologed thrombocytopeia ad preset a risk for meorrhagia... (page AYAO-6) Pregacy AYA wome diagosed with cacer durig pregacy require idividualized treatmet from a multidiscipliary team icludig medical, surgical ad radiatio ocologists, obstetricia, pathologist ad radiologist. Potetial beefits ad risks of chemotherapy ad RT for both the mother ad the fetus must be carefully evaluated before the start of treatmet. (page MS-8) Referral to a gyecologic ocologist ad periatologist with expertise ad kowledge of the physiological chages that occur durig pregacy is strogly recommeded. (page MS-8) Prevetio ad appropriate "Ideally, the decisio about Screeig Recommedatios for AYA Survivors... (page AYAO-B) treatmet of ifertility cadidacy for fertility preservatio Fertility preservatio should be a essetial part i the will be guided by a istitutioal maagemet of AYAs with cacer. Discuss the risk of ifertility policy ad shaped by a medical due to cacer therapy with all patiets at the time of diagosis... team, icludig a pediatric (page AYAO-6) ocologist, fertility specialist, ethicist, ad metal health professioal. (page e1466 ad throughout) [27] Prevetio, care ad Noe for STIs Provide health educatio about STIs, diet, ad exercise. treatmet of STIs: HPV vaccie HPV vaccie ca be (page AYAO-7) admiistered i these special Sice the icidece of STIs peaks amog AYAs years of age, circumstaces: a. whe a patiet provide prevetative health educatio about sexually trasmitted is immuocompromised because diseases. (page MS-10) of disease or medicatio... Recommed HPV immuizatio (if ot previously admiistered) (page 602) [29] for the prevetio of secodary cacers sice the vaccie has bee show to prevet cervical carcioma ad aal epithelial eoplasia, the precursor to carcioma. (page MS-10) Iformatio, educatio The adolescet or youg adult The impact of diagosis ad treatmet of cacer o their physical ad couselig o huma cacer survivor may be grapplig appearace, sexual developmet, ad sexual fuctio ca lead to sexuality ad reproductive with uique treatmet-related shame, social isolatio, ad regressive behaviors if ot addressed health health issues, such as ifertility, at promptly. (page MS 9) a time whe their sexual maturity ad persoal relatioships are developig. (page 66) Appropriate referrals for For survivors who are idetified Strogly cosider a referral for treatmet at a cacer ceter with further diagosis ad as havig chroic health problems expertise i treatmet of AYAs with cacer, ad have access to maagemet as a result of their previous cacer cliical trials for AYAs. (page AYAO 2) therapy, the pediatricia ca also Iitiate referral for fertility preservatio cliics withi 24 h for work with the primary ocology iterested patiets. (page AYAO-6) ceter to obtai assistace Referral to a gyecologic ocologist ad periatologist with with referrals to subspecialists expertise ad kowledge of the physiological chages that occur kowledgeable i issues related durig pregacy (ad impact cacer treatmet) is strogly to childhood cacer survivorship. recommeded. (page MS-8) (page 913) [9] Data take from [9]. Data take from [105]. AAP: America Academy of Pediatrics; AYA: Adolescet ad youg adult; HPV: Huma papillomavirus; NCCN: Natioal Comprehesive Cacer Network; RT: Radiotherapy; STI: Sexually trasmitted ifectio. 304 Cli. Pract. (2013) 10(3)

5 Reproductive health i adolescet & youg adult cacer populatios should avoid combied cotraceptive methods whe possible due to icreased risk of veous thromboembolism [14]. Eve whe a chemo therapeutic aget carries a high risk of ovaria failure (females) or azoospermia (males), ormal reproductive fuctio may recover post-treatmet [15,16]. Thus, the eed for cotraceptive plaig ad discussios may chage throughout the life spa of the AYA patiet. Curret evidece suggests that the NCCN ad AAP should cosider whether existig guidelies should be modified to tailor cotraceptive educatio ad choices to AYA ocology populatios, which icludes iformatio about the risks ad cotraidicatios as well as possible beefits. Pregacy The NCCN provides guidelies o pregacy durig treatmet amog AYA cacer patiets. The guidelies call for a idividualized, multi discipliary approach to maage the care of a pregat patiet o a case-by-case basis. Due to the limited data available regardig the cotiuatio of cacer treatmet as well as care for the fetus, the NCCN recommeds crosscare maagemet with a gyecologic ocologist. The AAP does ot address pregacy durig cacer treatmet. This places may physicias who rely o the AAP to guide cliical practice at a sigificat disadvatage. The AAP does, however, address adolescet pregacy i the geeral populatio. Cacer treatmets ad radiatio have kow teratogeic risks to a developig fetus, ragig from spotaeous abortio to cogeital malformatios [17,107]. Therefore, females who become pregat while o treatmet may have their pla of care sigificatly altered, or pregacy termiatio may be suggested [18,19]. Guidelies for discussios about the risks of becomig pregat while o treatmet, as well as cliical practice guidelies for the treatmet of pregat AYAs, should be available to physicias. The similarities betwee side effects of chemotherapy ad pregacy such as fatigue, ausea ad disruptio i meses ca cause a pregacy to be overlooked. This places the patiet ad developig fetus at a sigificat health risk. Ifertility It is well established that some cacer treatmets, such as alkylatig agets i chemotherapy, total-body radiatio or exteral-beam Guidelies Perspective radiatio i a field that icludes the ovaries or testes, may cause prologed or permaet ifertility i both males ad females. For postpubertal males, sperm cryopreservatio is the oly oexperimetal optio ad has the highest likelihood of success [20]. Froze sperm may the be thawed ad ijected ito a female parter or surrogate usig itracytoplasmic sperm ijectio or other types of assisted reproductive techology. For post pubertal females, embryo cryopreservatio, which ivolves fertilizig oocytes with sperm (door or parter) is the oly oexperimetal fertility preservatio optio [20,21]. The successful live birth rate from this method is approximately 50% [22]. A additioal optio for females is oophoropexy, where the ovaries are laparoscopically moved to a positio outside of the iteded radiatio field, but the success rate of this procedure has ot bee cliically established [23 25]. There are additioal experimetal fertility preservatio optios for males ad females. Testicular tissue cryopreservatio is available for pre- ad post-pubertal males, although at preset there are o reported live births usig this techique. Oocyte cryopreservatio (freezig of eggs) for postpubertal females is presetly cosidered a experimetal optio, however, i 2012, the America Society for Reproductive Medicie issued a statemet recommedig that the procedure be reclassified as oexperimetal due to the improved success rates [108]. Ovaria tissue cryopreservatio is aother experimetal optio for pre- ad post-pubertal females. Curretly, there are 13 kow live births that have resulted from the reimplatatio of cryopreserved ovaria tissue i adult wome [26]. While there are both established ad experimetal fertility preservatio optios for the AYA populatio, there are fiacial ad ethical issues with each optio, to be cosidered by patiets, family ad other stakeholders. The NCCN explicitly outlies the ecessity of physicias to discuss risks to fertility ad fertility preservatio optios with AYAs [105]. A flow chart is provided that guides physicias o how ad whe to systematically approach this discussio, icludig the duty of physicias to submit a referral to a reproductive professioal withi 24 h of the patiet s iterest. The AAP released a techical report i 2008 for AYA ocology physicias providig a comprehesive overview of risks to fertility, types, 305

6 Guidelies Perspective Qui, Murphy, Sehovic & Sawczy cost ad ethical issues of fertility preservatio [27]. This report additioally explais the role of the physicia to facilitate the discussio, ad offers guidace to ways this may be achieved. However, the AAP does ot iclude details regardig compromised reproductive potetial i the log-term follow-up guidelies. This is otable as ifertility is cosidered a late effect, however is ot icluded i the AAP s guidelies to maage late-oset complicatios. Eve so, the NCCN ad AAP have both provided guidelies to support the UNPF s missio of ifertility prevetio. A first step i the field of fertility ad ocology was the developmet of guidelies for adult cacer patiets by the Ethics Committee of the America Society for Reproductive Medicie i 2005 [28], ad the America Society of Cliical Ocology i 2006 [20], which detail the duty of ocologists to discuss risks to fertility from cacer or treatmet, ad also outlie established versus experimetal optios for fertility preservatio. Because fertility preservatio optios are most efficacious whe used prior to the iitiatio of therapy, the expasio of appropriate guidelies ito the AYA populatio is critical due to the frequet rush to start treatmet. Fertility preservatio optios vary by pubertal status, diagosis, age, locatio of the disease, dosage of treatmet ad pretreatmet fertility of the patiet, amog other factors. Whe cosiderig fertility preservatio, a persoalized approach to treatmet is paramout to educated decisio-makig. Prevetio, care & treatmet of STIs The NCCN provides recommedatios for admiistratio of the huma papillomavirus (HPV) vaccie for AYA cacer patiets i the supportive care guidelies. The NCCN specifically otes the beefit of protectig agaist future HPV-associated cacers, ad implies that despite the curret diagosis, patiets are at risk of developig other cacers. I this sese, the NCCN supports HPV immuizatio based o the recommedatios from the Advisory Committee o Immuizatio Practices for patiets 9 26 years old [107]. Similarly, the AAP has also itegrated the Advisory Committee o Immuizatio Practices HPV recommedatios ito the AAP HPV policy statemet [29]. The AAP s guidelies idicate that the vaccie may be give to patiets 306 Cli. Pract. (2013) 10(3) who are immuocompromised due to disease, as it is ot a live vaccie. This would iclude AYA cacer patiets. As the HPV recommedatios fall ito the age rage that characterizes AYAs, it is importat to discuss the justificatio for HPV immuizatio amog AYA cacer patiets ad survivors. It is somewhat expected for a patiet to be lymphopeic at multiple time poits throughout cacer care ad thus be particularly susceptible to ifectio. AYAs may be asymptomatic durig this time as well. For survivors, the threat of cotractig HPV is ever-preset. Some studies suggest that patiets who have udergoe allogeeic boe marrow trasplats as part of their cacer treatmet [19,30], have bee treated for Hodgki s lymphoma [31] ad treated with pelvic radiatio [32,33] have a icreased risk for cotractig HPV ad experiecig viral reactivatio as a result of immuosuppressio or therapy-related cervical tissue damage. Discussios of the HPV vacciatio should be a part of NCCN ad AAP guidelies for quality prevetative care. The NCCN addresses the issue of STIs amog AYA cacer patiets ad survivors i the available guidelies. The NCCN utilizes available data to imply that because the risk for STIs is greater amog geeral AYAs tha i other age groups, it should be recogized that AYAs with a history of cacer egage i risky sexual behavior at rates similar to their peers ad sibligs without cacer [11]. The AAP addresses STIs i multiple publicatios: cliical reports specific to males, guidelies specific to sexual educatio ad guidelies for overall health supervisio [34 36]. The overarchig otio is the ecessity for cosistet screeig practices. The AAP does ot address STIs i a ocology settig. Icludig STIs i stadard reproductive health discussios with AYA patiets ad survivors is critical. AYA survivors ad those udergoig cacer treatmet may be more physiologically susceptible to cotractig STIs due to a multitude of risk factors stemmig from compromised immue systems ad myelo suppressio. The impact of chemotherapy coupled with the log-term effects of STIs impairs the ability of the immue system to operate i the usual way, icreasig the risk of ifectio [37]. Furthermore, STIs ca cause damage to the reproductive system; chlamydia has bee show to produce blockage i the fallopia tube ad

7 Reproductive health i adolescet & youg adult cacer populatios cause ectopic pregacies as well as ifertility [38]. AYAs have a icreased health vulerability evideced by the high icidece rate of over 9 millio ew cases of STIs reported each year occurrig amog year olds [39]. The AAP should icorporate the UNFP s guidelies to esure this iformatio is ot missed for AYA ocology patiets. Iformatio, educatio & couselig o huma sexuality & reproductive health The NCCN briefly describes the role of huma sexuality for AYA ocology patiets throughout its guidelies. Table 1 highlights multiple areas of text where sexual idetity ad developmet are metioed. Largely, this iformatio is provided as part of the psychosocial impact of cacer, durig ad after treatmet, ad the recommedatio is for treatmet teams to be aware ad prepared to maage such experieces. The NCCN outlies the role of huma sexuality ad how these milestoes are ofte disrupted for AYA cacer patiets. However, this brief outlie lacks detail. The NCCN further explais the ecessity to moitor these issues throughout survivorship, ad cousel whe appropriate. The AAP has produced umerous policies ad recommedatios detailig the importace of attedig to issues of huma sexuality icludig sexual idetity [40] ad reproductive health specific to males [34]. However, huma sexuality ad persoal relatioships are oly briefly addressed i the log-term follow-up guidelies for pediatric cacer survivors. Couselig about issues related to huma sexuality is recogized by the UNPF ad should be recogized by the policies withi professioal AYA ocology orgaizatios. A variety of psychosocial issues are ecompassed withi huma sexuality, icludig body image, sexual orietatio, self-esteem ad egotiatios withi romatic relatioships, amog others [41,42]. Disruptios i these psycho sexual milestoes, such as with a cacer diagosis which ofte requires at least 3 years of cotiuous treatmet, are likely to reverberate throughout the lifespa ad impact quality of life [43]. Reproductive health issues beyod fertility for AYA cacer patiets should ot be eglected or assumed to be addressed withi guidelies for the geeral AYA populatio. Couselig efforts ad social itervetios should be specifically tailored for the developmetal stage Guidelies Perspective of the patiet, whe cacer is diagosed, to meet the eeds ad issues that the geeral AYA populatio does ot experiece. Appropriate referrals for further diagosis & maagemet The NCCN does a thorough job of idicatig that referrals eed to be made whe appropriate. Ragig from palliatio, to trasportatio, to disease specialists, there is cosistet laguage throughout the NCCN s AYA guidelies that referrals are ecessary for comprehesive cacer care. The NCCN highlights the beefits of the multidiscipliary team approach to AYA reproductive health maagemet, specifically as it relates to fertility, pregacy ad other areas of reproductive health. AAP guidelies are less forthcomig regardig appropriate referrals for reproductive health maagemet. AAP offers guidelies for pediatric cacer ceters i which referrals should be made to subspecialists whe appropriate [44]. Logterm follow-up guidelies provide a similar blaket statemet. The AAP does ot specify which psychosocial issues would potetially eed referral, however. The AAP does recommed appropriate referrals to fertility specialists for those of reproductive age i a separate policy statemet focused solely o fertility preservatio. There is a distict eed to refer AYA cacer patiets for maagemet of reproductive health. This icludes i-house referrals to social workers, psychologists, gyecologists or reproductive edocriologists if available. Referrals bridge the gap to reproductive health services that are traditioally ot icluded i ocology care. Sufficiet educatio for AYA ocology families also helps to improve rates of referrals by stimulatig a dialog about issues that patiets may ot otherwise be aware of [45]. Regardig fertility preservatio, rates of referral to fertility specialists for AYA cacer patiets are cosistetly low, citig the physicia s lack of ow kowledge ad iformatio [46,47]. A recet study suggests that the rate of referral for fertility preservatio ad couselig i youg wome diagosed with cacer may be lower amog those with less educatio or over the age of 35 years [48]. The authors report disparities i access to fertility preservatio services based o ethicity ad sexual orietatio as well. This is ufortuate because additioal research suggests that receivig couselig about fertility prior to the iitiatio of cacer treatmet 307

8 Guidelies Perspective Qui, Murphy, Sehovic & Sawczy has a sigificat improvemet i quality of life after cacer. Letoureau et al. assessed quality of life amog wome who had received fertility couselig from a specialist ad/or from their ocology team. Those who were couseled by a specialist ad attempted to preserve their fertility reported lower regret tha those who had bee couseled by their ocologists aloe [43]. The AYA cacer patiet is ot a majority populatio i pediatric or adult hospitals. Therefore, it is critical for professioal guidelies to recommed shared maagemet of care to esure specific quality-of-life idicators, such as reproductive health, are addressed. The divisio betwee what the NCCN ad what the AAP guidelies offer is importat to ucover as, for example, a pediatric ocologist treatig a 15 year old is likely to gravitate towards A AP guidelies, while a ocologist treatig a 39 year old at a comprehesive cacer ceter is likely to utilize the NCCN s guidelies; however, it is uclear if the ocologist gravitates towards either guidelies whe treatig a 25 year old. We ackowledge that a limitatio of our assessmet is that we did ot cosider the guidelies of other orgaizatios such the America Society of Cliical Ocology ad the Childre s Ocology Group to compare ad cotrast the metio of reproductive health issues beyod fertility from differet cliical perspectives. Primary care physicias who are iformatio-seekig have bee show to iitially rely o a colleague s expertise, the Refereces Feradez CV, Barr RD. Adolescets ad youg adults with cacer: a orphaed populatio. Paediatr. Child Health 11(2), (2006). Outlies that adolescets ad youg adults (AYAs) have a distict cacer epidemiology, evolvig hormoal milieu, maturig developmet, trasitios i autoomy, icreasig demads i educatio, etry ito the workplace ad family resposibilities. There is a eed for a specialized expertize to be required i carig for these patiets. I summary, the NCCN AYA ocology guidelies offer a more comprehesive approach to care ad itegrate the UNPF s refied reproductive health defiitio more successfully tha the AAP guidelies. A multidiscipliary approach is ecessary to bridge the gaps amog physicia practice guidelies. While may experts ad cosortium groups assist i developig such guidelies, resources for comprehesive care, particularly amog the AYA cacer populatio require uique coordiatio. Iitial itervetios such as cliical opiio pieces, systematic reviews ad further research ito AYA reproductive health should be udertake to motivate the revisio of curret AAP AYA ocology guidelies that broade the scope set forth by the UNPF. Fiacial & competig iterests disclosure The authors have o relevat affiliatios or fiacial ivolvemet with ay orgaizatio or etity with a fiacial iterest i or fiacial coflict with the subject matter or materials discussed i the mauscript. This icludes employmet, cosultacies, hooraria, stock owership or optios, expert t estimoy, grats or patets received or pedig, or royalties. No writig assistace was utilized i the productio of this mauscript. Gesudheit B, Greeberg ML, Kapelushik Y, Kore G. Drug compliace by adolescet cacer patiets. I: Cacer i Adolescets ad Youg Adults. Bleyer A, Barr R (Eds). Spriger-Verlag, Heidelberg, Germay (2005). 6 Treadgold CL, Kuperberg A. Bee there, doe that, wrote the blog: the choices ad challeges of supportig adolescets ad youg adults with cacer. J. Cli. Ocol. 28(32), (2010). 4 Goodma A. Treatig adolescets ad youg adults with cacer: special cocers. Ocology Times 24(8), (2002). 7 Wood EH. The Natioal Comprehesive Cacer Network (NCCN). J. Med. Libr. Assoc. 92(3), (2004). 5 Bellizzi KM, Smith A, Schmidt S et al. Positive ad egative psychosocial impact of beig diagosed with cacer as a adolescet or youg adult. Cacer 118(20), (2012). 8 Committee o Adolescece. Cotraceptio ad Adolescets. Pediatrics 120(5), (2007). 9 America Academy of Pediatrics Sectio o Hematology/Ocology Childre s Ocology Group. Log-term follow-up care for pediatric cacer survivors. Pediatrics 123(3), , (2009). Blever A. Cacer i older adolescets ad youg adults: epidemiology, diagosis, treatmet, survival, ad importace of cliical trials. Med. Pediatr. Ocol. 38(1), 1 10 (2002). Coclusio & future perspective 3 Papers of special ote have bee highlighted as: of iterest 1 will seek to aswer a questio usig established guidelies [49]. However, the mai complait from physicias is the time that must be spet o searchig for a aswer [50]. Explored the psychosocial impact of cacer o ewly diagosed AYA cacer patiets. The most prevalet areas of life impacted i a egative way were fiacial, body image, cotrol over life, work plas, relatioship with spouse/sigificat other ad plas for havig childre. Cli. Pract. (2013) 10(3) Systematic ogoig follow-up of childre, adolescets ad youg adults is importat for providig for early detectio of ad itervetio for potetially serious late oset

9 Reproductive health i adolescet & youg adult cacer populatios complicatios. I additio, health couselig ad promotio of healthy lifestyles are importat aspects of log-term follow-up care The Coucil o Commuicatios ad Media. Policy Statemet: Sexuality, cotraceptio, ad the media. Pediatrics 126(3), (2010) Marcell AV, Wibbelsma C, Seigel WM; the Committee o Adolescece. Cliical report: male adolescet sexual ad reproductive health care. Pediatrics 128(6), e1658 e1676, (2011) Arikoski P, Komulaie J, Riikoe P et al. Impaired developmet of boe mieral desity durig chemotherapy: a prospective aalysis of 46 childre ewly diagosed with cacer. J. Boe Mier. Res. 14, (1999). Maltaris T, Seufert R, Fischl F et al. The effect of cacer treatmet o female fertility ad strategies for preservig fertility. Eur. J. Obstet. Gyecol. Reprod. Biol. 130, (2007). Committee o Psychosocial Aspects of Child ad Family Health ad Committee o Adolescece. Sexuality educatio for childre ad adolescets. Pediatrics 108(2), (2001) Williams RS, Medehall N. Laparoscopic oophoropexy for preservatio of ovaria fuctio before pelvic ode irradiatio. Obstet. Gyecol. 80, 541 (1992). America Academy of Pediatrics, Committee o Psychosocial Aspects of Child ad Family Health. Guidelies for Health Supervisio III. America Academy of Pediatrics, IL, USA (1997). 25 Tereziai M, Piva L, Meazza C, Gadola L, Cefalo G, Merola M. Oophoropexy: a relevat role i preservatio of ovaria fuctio after pelvic irradiatio. Fertil. Steril. 91, e915 e935 (2009). 37 Weistock H, Berma S, Cates W Jr. Sexually trasmitted diseases amog america youth: icidece ad prevalece estimates, Perspect. Sex Reprod. Health 36, 6 10 (2004) Doez J, Silber S, Aderse CY et al. Childre bor after autotrasplatatio of cryopreserved ovaria tissue. a review of 13 live births. A. Med. 43(6), (2011). Coste J, Laumo B, Brémod A, Collet P, Job-Spira N. 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Cacer 118(6), (2012). 44 Corriga JJ, Feig SA; America Academy of Pediatrics. Guidelies for pediatric cacer ceters. Pediatrics 113(6) (2004). 45 Bleyer A. Adolescet ad youg adult (AYA) ocology. Pediatr. Hematol. Ocol. 24(5), (2007). 46 Qui GP, Vadaparampil ST; Fertility Preservatio Research Group. Fertility preservatio ad adolescet/youg adult Patel A, Schwarz EB; Society of Family Plaig. Cacer ad cotraceptio. Cotraceptio 86(3), (2012) Klosky JL, Howell CR, Li Z, Foster RH, Mertes AC, Robiso LL, Ness KK. Risky health behavior amog adolescets i the childhood cacer survivor study cohort. J. Pediatr. Psychol. 37(6), (2012) Oktay K, Beck L, Reiecke J. Oe Hudred Questios ad Aswers About Cacer ad Fertility. Joes ad Bartlett, MA, USA (2008). Fujimura M, Ostrow RS, Okagaki T. Implicatio of huma papillomavirus i postirradiatio dysplasia. Cacer 68(10), (1991). Malizia B, Hacker M, Pezias A. Cumulative live-birth rates after i vitro fertilizatio. N. Egl. J. Med. 360, (2009). Harel Z, Cromer B. 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Ocol. 24(18), (2006). As part of educatio ad iformed coset before cacer therapy, ocologists should address the possibility of ifertility with patiets treated durig their reproductive years ad be prepared to discuss possible fertility preservatio optios or refer 28 This techical report reviews the topic of fertility preservatio i pediatric ad adolescet patiets with cacer, icludig ethical cosideratios. Ethics Committee of the America Society for Reproductive Medicie. Fertility preservatio ad reproductio i cacer patiets. Fertil. Steril. 83(6), (2005). 29 Committee o Ifectious Diseases. HPV vaccie recommedatios. Pediatrics 129(3), (2012). 30 Bhatia S, Louie AD, Bhatia R et al. Solid cacers after boe marrow trasplatatio. J. Cli. Ocol. 19(2), (2001). 31 Serraio D, Fraceschi S, Talamii R et al. Socio-ecoomic idicators, ifectious diseases ad Hodgki s disease. It. J. Cacer 47(3), (1991). 32 Barzo L, Pizzighella S, Corti L, Megoli C, Palù G. Vagial dysplastic lesios i wome with hysterectomy ad receivig radiotherapy are liked to high-risk huma papillomavirus. J. Med. Virol. 67(3), (2002)

10 Guidelies Perspective Qui, Murphy, Sehovic & Sawczy cacer patiets: physicia commuicatio challeges. J. Adolesc. Health 44(4), (2009) Schover LR, Brey K, Lichti A et al. Ocologists attitudes ad practices regardig bakig sperm before cacer treatmet J. Cli. Ocol. 20, (2002). Letoureau JM, Smith JF, Ebbel EE et al. Racial, socioecoomic, ad demographic disparities i access to fertility preservatio i youg wome diagosed with cacer. Cacer 118(18), (2012). Gorma Iformatio eeds i primary care: a survey of rural ad orural primary care physicias. Stud. Health Techol. Iform. 84(Pt 1), (2001). Butzlaff M, Vollmar HC, Floer B, Koeczy N, Isfort J, Lage S. Learig with computerized guidelies i geeral practice? A radomized cotrolled trial. Fam. Pract. 21(2), (2004). guidelies.asp Websites 101 CDC. Defiito of Health-Related Quality of Life (HRQOL) Natioal Cacer Istitute. A sapshot of adolescet ad youg adult cacers. sapshots/aya.pdf 103 WHO. Health topics. Reproductive health UNFPA. Makig reproductive rights ad sexual ad reproductive health a reality for all. Reproductive rights ad sexual ad reproductive health framework (2011). documets/unfpa_srh_framework_ FialVersio.pdf 105 Natioal Comprehesive Cacer Network, Ic. NCCN Cliical Practice Guidelies i Ocology. Adolescet ad Youg Adult (AYA) Ocology. Versio Cli. Pract. (2013) 10(3) Natioal Comprehesive Cacer Network guidelies are widely recogized ad used as the stadard for cliical policy i ocology by cliicias ad payors. 106 WHO. Medical eligibility criteria for cotraceptive use (4th Editio) (2010). publicatios/2010/ _eg.pdf 107 CDC. Press release: CDC s Advisory Committee recommeds huma papillomavirus virus vacciatio. r htm 108 America Society of Reproductive Medicie. Press release. Fertility experts issue ew report o egg freezig; ASRM lifts experimetal label from techique. New_Report_o_Egg_Freezig_ASRM_ Lifts_Experimetal_Label_from_Techique