Fertility preservation for female 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; Hudson, Melissa M.; Santen, Hanneke M van; Loeffen, Erik A. H.; Burns, Karen; Quinn, Gwendolyn P.; Broeder, Eline van Dulmen‐den; Byrne, Julianne; Haupt, Riccardo; Wallace, William H.; Heuvel‐Eibrink, Marry M. van den; Anazodo, Antoinette; Anderson, Richard A.; Barnbrock, Anke; Beck, Jöern D.; Bos, Annelies M E; Demeestere, Isabelle; Denzer, Christian; Iorgi, Natascia Di; Hoefgen, Holly; Kebudi, Rejin; Lambalk, Cornelis B.; Langer, Thorsten; Meacham, Lillian R.; Rodriguez‐Wallberg, Kenny A.; Stern, Catharyn; Stutz-Grunder, Eveline; Dorp, Wendy van; Veening, Margreet A.; Veldkamp, Saskia R.; Meulen, Eline van der; Constine, Louis S.; Kenney, Lisa B.; Wetering, Marianne D. van de; Kremer, Leontien C. M.; Levine, Jennifer; Tissing, Wim J. E.; Berger, Claire; Diesch, Tamara; Dirksen, Uta; Ginsberg, Jill P.; Giwercman, Aleksander; Grabow, Desiree; Gracia, Clarisa R.; Hunter, Sarah; Inthorn, Julia; Kaatsch, Peter; Kelvin, Joanne Frankel; Klosky, James L.; Laven, Joop S.E.; Lockart, Barbara; Neggers, Sebastian J C M M; Paul, Norbert W.; Peate, Michelle; Phillips, Bob; Reed, Damon R.; Tinner, Eva Maria; Berg, M. van den; Verhaak, Chris M.

doi:10.1016/s1470-2045(20)30594-5

Cited by 110 publications

(115 citation statements)

References 81 publications

(170 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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“…Additionally, vascular damage, stromal injury or fibrosis may occur. To calculate the gonadotoxic risk [70][71][72], the patient should receive an equivalent dose of CFM (cyclophosphamide equivalent dose, CED) according to the formula of Green et al: > 6000-8000 mg/ m 2 in women and > 4000 mg/m 2 in men, ovarian or testicular RT or HSCT (73). The following equivalences were used (CFM = 1; ifosfamide × 0.244; procarbazine × 0.857; chlorambucil × 14.28; BCNU × 16; melphalan × 40; thiotepa × 40; nitrogen mustard × 100; busulfan × 8.82).…”

Section: Chemotherapymentioning

confidence: 99%

Multidisciplinary consensus on the criteria for fertility preservation in cancer patients

et al. 2021

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Infertility is one of the main sequelae of cancer and its treatment in both children and adults of reproductive age. It is, therefore, essential that oncologists and haematologists provide adequate information about the risk of infertility and the possibilities for its preservation before starting treatment. Although many international clinical guidelines address this issue, this document is the first Spanish multidisciplinary guideline in paediatric and adult oncological patients. Experts from the Spanish Society of Medical Oncology, the Spanish Fertility Society, the Spanish Society of Haematology and Haemotherapy, the Spanish Society of Paediatric Haematology and Oncology and the Spanish Society of Radiation Oncology have collaborated to develop a multidisciplinary consensus.

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Fertility preservation for female 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 110 publications

References 81 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

Multidisciplinary consensus on the criteria for fertility preservation in cancer patients

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