Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group

Mulder, Renée L.; Font-Gonzalez, Anna; Broeder, Eline van Dulmen‐den; Quinn, Gwendolyn P.; Ginsberg, Jill P.; Loeffen, Erik A. H.; Hudson, Melissa M.; Burns, Karen; Santen, Hanneke M van; Berger, Claire; Diesch, Tamara; Dirksen, Uta; Giwercman, Aleksander; Gracia, Clarisa R.; Hunter, Sarah; Kelvin, Joanne Frankel; Klosky, James L.; Laven, Joop S.E.; Lockart, Barbara; Neggers, Sebastian J C M M; Peate, Michelle; Phillips, Bob; Reed, Damon R.; Tinner, Eva Maria; Byrne, Julianne; Veening, Margreet A.; Berg, Marleen van de; Verhaak, Chris M.; Anazodo, Antoinette; Rodriguez‐Wallberg, Kenny A.; Heuvel‐Eibrink, Marry M. van den; Asogwa, Ogechukwu Augustina; Brownsdon, Alexandra; Wallace, William H.; Green, Daniel M.; Skinner, Roderick; Haupt, Riccardo; Kenney, Lisa B.; Levine, Jennifer; Wetering, Marianne D. van de; Tissing, Wim J. E.; Paul, Norbert W.; Kremer, Leontien C. M.; Inthorn, Julia; Anderson, Richard A.; Barnbrock, Anke; Beck, Jöern D.; Bos, Annelies M E; Calaminus, Gabriele; Constine, Louis S.; Demeestere, Isabelle; Denzer, Christian; Grabow, Desiree; Iorgi, Natascia Di; Hoefgen, Holly; Jahnukainen, Kirsi; Kaatsch, Peter; Kebudi, Rejin; Lambalk, Cornelis B.; Langer, Thorsten; Loonen, Jacqueline; Lorenzo, Armando J.; Meacham, Lillian R.; Meißner, Andreas; Mitchell, Rod; Nahata, Leena; Ranft, Andreas; Dinkelman-Smit, Marij; Stern, Catharyn; Stutz-Grunder, Eveline; Tournaye, Herman; Dorp, Wendy van; Pelt, Ans M.M. van; Vries, Andrica de; Yu, Richard N.

doi:10.1016/s1470-2045(20)30595-7

Cited by 40 publications

(29 citation statements)

References 121 publications

(308 reference statements)

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“…First, regarding primary hypogonadism, it is essential to discuss with the patient the possibility of altered gametogenesis and the subsequent reduced fertility. Accordingly, fertility-preservation strategies 62 , 63 , 64 (gamete cryopreservation) should be offered, especially in the curative setting where a cure can be achieved and family planning can be made. Although such a strategy could be pursued in a metastatic setting, it is better to avoid a delayed therapy initiation in favor of a fertility-preservation strategy, especially in high-burden disease.…”

Section: Current Clinical Practicesmentioning

confidence: 99%

Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

2021

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Immune checkpoint inhibitors (i.e. anti-PD1, anti-PDL1, and anti-CTLA4) have revolutionized the therapeutic approach of several cancer types. In a subset of metastatic patients, the duration of the response is so long that a cure might be hypothesized, and a treatment discontinuation strategy could be proposed. Considering that long-term efficacy, some patients could also plan to have a child. Moreover, immunotherapy is moving to the early setting in several diseases including melanoma and breast cancer that are common cancers in young patients. However, there is a paucity of data about their potential detrimental effect on fertility, pregnancy, or sexuality. Herein, we conducted a systematic review with the aim to comprehensively collect the available evidence about fertility, pregnancy, and sexual adverse effects of checkpoint inhibitors in order to help clinicians in daily practice and trialists to develop future studies.

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Section: Current Clinical Practicesmentioning

confidence: 99%

Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

2021

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“…Our findings may enhance clinical practice by identifying patients at high risk of ovarian impairment who more than others may benefit from referral and counseling about fertility preservation options. Recently, the International Guideline Harmonisation Group (IGHG) published recommendations advising that all patients should be informed about their potential risk of gonadal damage [ 74 , 75 , 76 ]. This is in line with the current views and wishes of both healthcare providers and patients and their families [ 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Genetic Variation in CYP450 on Gonadal Impairment in a European Cohort of Female Childhood Cancer Survivors, Based on a Candidate Gene Approach: Results from the PanCareLIFE Study

Perk

Broer

Yasui

et al. 2021

Cancers

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Background: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to evaluate associations between previously identified genetic polymorphisms in CYP450 enzymes and AA-related ovarian function among adult CCSs. Methods: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in a discovery cohort of adult female CCSs, from the pan-European PanCareLIFE cohort (n = 743; age (years): median 25.8, interquartile range (IQR) 22.1–30.6). Using two additive genetic models in linear and logistic regression, nine genetic variants in three CYP450 enzymes were analyzed in relation to cyclophosphamide equivalent dose (CED) score and their impact on AMH levels. The main model evaluated the effect of the variant on AMH and the interaction model evaluated the modifying effect of the variant on the impact of CED score on log-transformed AMH levels. Results were validated, and meta-analysis performed, using the USA-based St. Jude Lifetime Cohort (n = 391; age (years): median 31.3, IQR 26.6–37.4). Results: CYP3A4*3 was significantly associated with AMH levels in the discovery and replication cohort. Meta-analysis revealed a significant main deleterious effect (Beta (95% CI): −0.706 (−1.11–−0.298), p-value = 7 × 10−4) of CYP3A4*3 (rs4986910) on log-transformed AMH levels. CYP2B6*2 (rs8192709) showed a significant protective interaction effect (Beta (95% CI): 0.527 (0.126–0.928), p-value = 0.01) on log-transformed AMH levels in CCSs receiving more than 8000 mg/m2 CED. Conclusions: Female CCSs CYP3A4*3 carriers had significantly lower AMH levels, and CYP2B6*2 may have a protective effect on AMH levels. Identification of risk-contributing variants may improve individualized counselling regarding the treatment-related risk of infertility and fertility preservation options.

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“…Effects of Childhood Cancer Guideline Harmonisation Group, have been produced. [9][10][11] Several countries have published their own guidance on fertility preservation including the American Society of Clinical Oncology (ASCO), 12 13 Children's Cancer and Leukaemia Group, 14 Children's Oncology Group 15 and the British Fertility Society (BFS). 16 Within the UK, paediatric cancer services are delivered through 20 specialist Principal Treatment Centres (PTCs).…”

Section: Original Researchmentioning

confidence: 99%

Inconsistencies in fertility preservation for young people with cancer in the UK

et al. 2021

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ObjectiveTo assess the utilisation of and funding structure for fertility preservation for children diagnosed with cancer in the UK.DesignSurvey of paediatric oncologists/haematologists. Questionnaires were sent electronically with reminder notifications to non-responders.SettingUK Paediatric Oncology Principal Treatment Centres (PTCs).ParticipantsPaediatric oncologists/haematologists with an interest in the effects of treatment on fertility representing the 20 PTCs across the UK.Main outcome measuresReferral practices, sources and length of funding for storage of gametes or gonadal tissue for children diagnosed with cancer in the preceding 12 months.ResultsResponses were received from 18 PTCs (90%) with responses to 98.3% of questions. All centres had referred patients for fertility preservation: ovarian tissue collection/storage 100% (n=18 centres), sperm banking 100% (n=17; one centre was excluded due to the age range of their patients), testicular tissue storage 83% (n=15), mature oocyte collection 35% (n=6; one centre was excluded due to the age range of their patients). All centres with knowledge of their funding source reported sperm cryopreservation was NHS funded. Only 60% (n=9) centres reported the same for mature oocyte storage. Of the centres aware of their funding source, half reported that ovarian and testicular tissue storage was funded by charitable sources; this increased in England compared with the rest of the UK.ConclusionsInequality exists in provision of fertility preservation for children with cancer across the UK. There is lack of formalised government funding to support international guidelines, with resultant geographical variation in care. Centralised funding of fertility preservation for children and young adults is needed alongside establishment of a national advisory panel to support all PTCs.

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Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group

Cited by 40 publications

References 121 publications

Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

Effect of Genetic Variation in CYP450 on Gonadal Impairment in a European Cohort of Female Childhood Cancer Survivors, Based on a Candidate Gene Approach: Results from the PanCareLIFE Study

Inconsistencies in fertility preservation for young people with cancer in the UK

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