Abstract

Abstract Study question Do breast cancer (BC) prognostic factors influence ovarian reserve and response to controlled ovarian hyperstimulation (COH) in the context of fertility preservation (FP)? Summary answer BC prognostic factors do not influence ovarian reserve and response to COH in the context of FP. What is known already Tumor Grade, triple-negative status, overexpression of HER2, as well as high Ki67 expression are all established prognostic factors for BC, influencing patients’ therapeutic management. Yet, there are still concerns about the potential impact of cancer status on ovarian reserve and response to COH. Previous studies analyzing the results of COH in BC patients have shown conflicting findings. However, there is limited data on the potential impact of BC status and prognostic factors on ovarian reserve and response to ovarian stimulation in women undergoing urgent FP. Study design, size, duration Observational, bicentric retrospective study including all BC patients who had vitrified oocytes after COH using a random start GnRH antagonist protocol after measurement of serum AMH levels and antral follicle count (AFC) between November 2013 and August 2021. Participants/materials, setting, methods Three-hundred-fifty-two BC patients having undergone one cycle of COH were analyzed. Number of oocytes recovered, maturation rate (number of mature oocytes/number of oocytes recovered), and Oocyte Retrieval Rate (number of retrieved oocytes/AFC) were studied according to the patients’ general characteristics, ovarian reserve markers, as well as BC diagnostic and prognostic factors: histological type, uni/multifocal character, TNM or UICC stage, hormonal receptors expression, HER2 status, Ki67, Grade, presence of vascular emboli, lymph node and BRCA1/2 status. Main results and the role of chance Overall, mean patients’ age was 33.6 ± 4 years. Mean AFC and serum AMH level were 20.5 ± 13.0 follicles and 2.7 ± 4.6 ng/mL, respectively. After ovarian stimulation, 12.5 ± 8.5 oocytes were recovered and 9.3 ± 6.9 were mature and further vitrified. Mean oocyte maturation rate was 74 ± 23%. As expected, patient’s age was significantly related to the number of mature oocytes recovered. Indeed, the risk of yielding less than 8 oocytes increased significantly after the age of 35 years. In addition, the oocyte maturation rate was also significantly higher before the age of 30 years, with an OR of 0.64 (0.43-0.96) to obtain a maturation rate <60%. Follicular responsiveness to FSH assessed by the follicular output rate (FORT index) as well as OOR were 30 ± 24% and 61 ± 27%, respectively, and both indexes were not influenced by tumor characteristics. However, maturation rate <60% was significantly related to SBR grade (OR = 0.73 (0.54-0.97), p<0.03) and the presence of a BRCA1/2-mutation (OR = 0.64 (0.42-0.99), p<0.03). Limitations, reasons for caution The main weakness is the retrospective nature of the study. Furthermore, the lack of data on reutilization of oocytes after FP prevents drawing reliable conclusions on the fate of these frozen gametes. Wider implications of the findings Our findings indicate that BC prognostic factors do not influence ovarian reserve markers nor the response to ovarian stimulation in the context of FP. Therefore, tumor grade, triple-negative status, overexpression of HER2, and high Ki67 should not modify the FP strategy when COH for oocyte vitrification is considered. Trial registration number N/A

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