Affiliation:
1. Cancer Therapies, Stem Cell Medicine Murdoch Children's Research Institute Parkville Victoria Australia
2. Department of Obstetrics, Gynaecology and Newborn Health Royal Women's Hospital, University of Melbourne Parkville Victoria Australia
3. Department of Paediatrics University of Melbourne Parkville Victoria Australia
4. Reproductive Development Murdoch Children's Research Institute Parkville Victoria Australia
5. Victorian Clinical Genetics Services Murdoch Children's Research Institute Melbourne Victoria Australia
6. Gynaecology, Royal Children‘s Hospital Parkville Victoria Australia
7. Reproductive Services, The Royal Women's Hospital Parkville Victoria Australia
8. Children's Cancer Centre, The Royal Children's Hospital Parkville Victoria Australia
Abstract
AbstractFor the same age, sex, and dosage, there can be significant variation in fertility outcomes in childhood cancer survivors. Genetics may explain this variation. This study aims to: (i) review the genetic contributions to infertility, (ii) search for pharmacogenomic studies looking at interactions of cancer treatment, genetic predisposition and fertility‐related outcomes. Systematic searches in MEDLINE Ovid, Embase Classic+Embase, and PubMed were conducted using the following selection criteria: (i) pediatric, adolescent, and young adult cancer survivors, below 25 years old at the time of diagnosis, (ii) fertility outcome measures after cancer therapy, (iii) genetic considerations. Studies were excluded if they were (i) conducted in animal models, (ii) were not published in English, (iii) editorial letters, (iv) theses. Articles were screened in Covidence by at least two independent reviewers, followed by data extraction and a risk of bias assessment using the Quality in Prognostic Studies tool. Eight articles were reviewed with a total of 29 genes. Outcome measures included sperm concentration, azoospermia, AMH levels, assessment of premature menopause, ever being pregnant or siring a pregnancy. Three studies included replication cohorts, which attempted replication of SNP findings for NPY2R, BRSK1, FANCI, CYP2C19, CYP3A4, and CYP2B6. Six studies were rated with a high risk of bias. Differing methods may explain a lack of replication, and small cohorts may have contributed to few significant findings. Larger, prospective longitudinal studies with an unbiased genome‐wide focus will be important to replicate significant results, which can be applied clinically.