Effectiveness of Controlled Ovarian Stimulation for Oocyte Preservation in Oncologic Patients: Insights from DuoStim Protocol

<b>Background/Objectives</b>: Fertility preservation is a key component of oncological care. This study evaluated the effectiveness of different controlled ovarian stimulation (COS) protocols, including dual stimulation (DuoStim), for oocyte preservation, with a specific focus on breast cancer patients, and aimed to identify predictors of mature oocyte yield. <b>Methods</b>: A retrospective single-center study was conducted on 203 women under 40 years undergoing fertility preservation before cancer treatment between August 2013 and May 2024 at the Fertility Unit of the University Hospital of Pisa. COS protocols were stratified by menstrual cycle phase: early follicular (EFP), late follicular (LFP), luteal (LP), and DuoStim. The primary outcome was fertility preservation, assessed by the number of mature oocytes retrieved (MII). Independent predictors of oocyte yield were assessed using multivariable Poisson regression. <b>Results</b>: A total of 244 COS cycles were analyzed. The DuoStim group showed a lower median number of MII oocytes collected during the second stimulation compared to EFP, LFP, and LP (all adjusted <i>p</i>-value < 0.05, FDR); however, cumulative MII counts across both stimulations were comparable to other protocols. Oocyte maturity rates were similar across groups. Multivariable analysis identified AMH and AFC, but not age, basal FSH, hormonal parameters, and year of cryopreservation, as independent predictors of MII oocyte yield. <b>Conclusions</b>: COS is effective for fertility preservation across different cycle phases without delaying cancer treatment. DuoStim is not inferior but rather a valuable strategy for poor responders with insufficient oocyte yield after an initial cycle, thereby broadening opportunities for cryopreservation in time-sensitive oncological settings.