Fertility in female cancer survivors: a systematic review and meta-analysis

Study question: What are the chances of female survivors of different types of cancer to fulfil their reproductive desire? Summary answer: Bone, breast, brain and kidney cancer survivors have reduced chances of childbirth.Womenwith thyroid cancer,melanoma and NonHodgkin lymphoma can be reassured. What is known already: Several epidemiological studies investigated the effects of cancer therapies on fertility considering the chances of pregnancy and childbirth as primary outcomes. However, conflicting data have been reported for the different cancer sites and a global interpretation of the results is not possible due to the different weight of the individual studies. In the absence of a data synthesis, at present, it is therefore not possible to provide an accurate counselling to patients on the fertility damage of oncological treatments and to share decisions regarding fertility preservation options. Study design, size, duration: The present systematic review and meta-analysis was restricted to published research articles that investigated the chances of pregnancy or live birth in women after treatment of different types of cancer (i.e. leukaemia, breast cancer, Hodgkin lymphoma, Non Hodgkin lymphoma, brain cancer, soft tissue cancer, liver cancer, digestive tract cancer, kidney cancer, thyroid cancer). We systematically searched Pubmed, MEDLINE, Embase and Scopus, from database inception to January 15, 2019. The study is registered with PROSPERO (CRD42019119786). Participants/materials, setting, methods: The literature overview was reported according to the PRISMA guidelines. Published cohort, case-control and cross-sectional studies were eligible for inclusion. All pertinent articles were retrieved, and the relative reference lists were reviewed. Studies were excluded if: (i) crude or adjusted effect estimates with corresponding 95%CIs or results allowing their calculation were not reported, (ii) control population was not clearly defined. The quality of casecontrol and cohort studies was evaluated by means of the Newcastle-Ottawa scale. Main results and the role of chance: Our searches identified 41 non-duplicate records, of which 18 relevant studies were included in the qualitative and quantitative analysis. Childbirth chances resulted significantly reduced in women with a history of bone cancer (HR 0.86, 95%CI[0.77-0.97]; I2=0%; p=0.02; RaR 0.76, 95%CI[0.61- 0.95]; I2=69%; p=0.01), breast cancer (HR 0.74, 95%CI[0.61-0.91]; RaR 0.51, 95%CI[0.47-0.57]; I2=0%; p<0.00001), brain cancer (HR 0.61, 95%CI[0.53- 0.70]; I2=14%; p<0.00001; RaR 0.44, 95%CI[0.33-0.60]; I2=95%; p<0.00001; OR 0.49, 95%[0.40-0.60; RR 0.62; 95%CI [0.42-0.91]; p=0.02) and kidney cancer (RaR 0.69, 95%CI[0.61-0.78]; p<0.00001; RR 0.66; 95%CI [0.43- 0.98]; p=0.04). Data pooling showed conflicting results in soft tissue cancer, Hodgkin lymphoma, and leukaemia patients. Reproductive chances in women survived from Non Hodgkin lymphoma, melanoma and thyroid cancer resulted unaffected. Limitations, reasons for caution: Most of the studies did not report detailed information on the characteristics of the oncologic treatments. Possible lurking variables should also be considered. In fact, physical and psychological sequelae of such aggressive therapies may affect the relationship life confounding the association between cancer or cancer treatment and fertility. Wider implications of the findings: WomNNen are currently informed providing data on the chemotherapy effects on poorly reliable fertility markers and on the reproductive chances cumulatively calculated for many cancer sites. Estimates by type of cancer are therefore of utmost importance to counsel patients and to assess the riskbenefit ratio before starting fertility preservation programs. Trial registration number: N.A.