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 starti