Abstract

Abstract Study question What is the impact of fertility preservation (FP) procedures and cancer treatment on relapse, survival, ovarian damage and pregnancy outcomes in oncological patients? Summary answer FP technique (including ovarian stimulation for oocyte vitrification) does not affect relapse or survival rates even in hormone dependant tumours. What is known already FP has become a crucial part of oncological evaluation of young women facing cancer given the high survival rates achieved. Oocyte vitrification (OV) and ovarian cortex cryopreservation (OCC) are the main techniques offered to these patients at the moment. However, information on the true incidence of premature ovarian insufficiency (POI), return rates to use the cryopreserved material and the natural pregnancy rates achieved in these patients is still limited. Moreover although there is some data about the safety of these techniques the impact of FP on disease survival is yet to be definitely assessed. Study design, size, duration Prospective cohort study. 695 patients enrolled since 2001 until 2016. Patients referred to FP unit in a public hospital setting (Hospital Peset Valencia 2001-2006 and University Hospital La Fe 2007-2016). After evaluation 556 patients received a FP technique (OV, OCC or embryo vitrification ) and 139 patients did not receive any due to medical reasons or patient’s choice. Minimum follow-up 5 years after enrolment Participants/materials, setting, methods Baseline characteristics including type of cancer and previous chemotherapy at diagnosis and prior to FP technique were recorded followed by risk of chemotherapy treatment received, relapse, survival, POI and poor ovarian reserve (POR) occurrence and pregnancy outcomes. Primary outcome was median survival time after FP in months. Secondary outcomes included relapse rate, POI and POR incidence, usage FP rate, clinical pregnancy and live birth (LB) rates naturally and after FP use. Main results and the role of chance There were no differences in survival comparing patients undergoing FP versus no FP (median 89.67 vs 92.81 months, p = 0.3). However, patients that used their cryopreserved material survived more than those who did not (97.3 vs 89.5, p = 0.012). When assessing survival rates comparing patients that had approval to get pregnant versus those who did not we found a higher survival in the former (98.84 vs 84.79 months, p < 0.001). Breast cancer patients with hormone dependent tumors undergoing ovarian stimulation for OV vs OCC had no differences in survival (95.62 vs 87.38 months, p = 0.37). POI incidence was 20.29% (N = 141). POI patients were significantly older (32.28 vs 29.63, p < 0.001) and had received high-risk chemotherapy more frequently (31.74% vs 2.27%, p < 0.001). Ovarian damage incidence (including also POR) was 48.06% (N = 334). Eighty-six patients (15.47%) used their cryopreserved material. Among the patients with pregnancy wish (N = 266) there were 84 spontaneous live births (31.58%). Patients that conceived naturally were significantly younger (30.71 vs 33.46, p < 0.001) and the chemotherapy received was more frequently low-risk (43.20% vs 23.52%, p = 0.018). There were 37 LB after use of FP (37/86, 43.02%). Patients with a higher ovarian reserve percentile had a higher chance of achieving a natural LBR (OR 1.016, 1.005-1.027, p = 0.004) Limitations, reasons for caution The higher survival found in patients using their cryopreserved material is mediated by the prognosis of the disease itself that limits the chance of pregnancy to those with a stable disease. Wider implications of the findings FP does not have a negative impact on survival even if ovarian stimulation is used. Almost half of the patients had ovarian damage (POI or POR) as a result of treatment; this is higher than previously reported. Among the patients with fertility wish around one third achieved a LB naturally. Trial registration number not applicable

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