Long-term follow up to assess criteria for fertility preservation in young women and girls with cancer

Background
Most young women and girls treated for cancer will retain fertility, but in some, treatment causes premature ovarian insufficiency (POI) with fertility loss. It is essential to identify those at risk and consider fertility preservation options. Ovarian tissue cryopreservation (OTC) has been offered since 1996 using specific criteria to identify patients at high risk of POI. Long-term follow up of reproductive outcomes is necessary to validate and refine these criteria.

Methods
Reproductive status of all females (up to age 18 years) diagnosed with cancer in South East Scotland between 1st January 1996 and 30th June 2012 was assessed using clinical records. Primary outcome was robust evidence of POI.

Results
Records of 321 of 407 patients aged 12 years or over were analysed. Patients on hormonal contraception (n=6) were excluded, giving a study population of 315. Mean age at diagnosis was 7.8 and at analysis 24.2 years. Median duration of follow up was 10.3 years (range 0-24 years). 27 (8.6%) patients had been offered OTC as per the Edinburgh selection criteria. 109 patients had unknown reproductive status but were included in the analysis and assumed to not have POI. Of the 27 patients offered OTC, 7 (25.9%) had developed POI. In the 288 not offered OTC, 6 (2.1%) developed POI (p<0.0001), 5 of whom had required further treatment for disease relapse.

Conclusions
This long-term follow up analysis demonstrates the low overall prevalence of POI after treatment for childhood cancer. Whilst the Edinburgh selection criteria are shown to be a valid and accurate assessment tool to identify those at risk at the time of diagnosis, the issue of disease relapse and subsequent gonadotoxic treatment remains challenging. The analysis also highlights gaps in recording gonadal function, which should be a standard part of long-term oncology follow up.