We report a rare case of ovarian hyperstimulation syndrome (OHSS) in a 28-year-old woman with breast cancer and with a history of polycystic ovary syndrome (PCOS) despite treatment with letrozole and gonadotropin-releasing hormone agonist (GnRH-a) triggering in a GnRH antagonist (GnRH-ant) protocol without the administration of any human chorionic gonadotropin (hCG) for luteal-phase support. The patient, who underwent controlled ovarian syndrome (COS)-oocyte cryopreservation before chemotherapy, required hospitalization. Complete recovery was achieved after treatment with volume expanders, human albumin, and cabergoline. Based on our case and literature review, it is possible to establish that estradiol (E2) modulation with letrozole and GnRH-a triggering does not eliminate the risk of OHSS. Furthermore, it is advisable to postpone GnRH-a depot to minimize the risk of OHSS after the suspension of letrozole, following menstruation or at least 7–8 days after triggering. It would be desirable to identify high-risk patients, also on a genetic basis, in order to avoid delays in oncologic treatments that could strongly impact life expectancy.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication associated with controlled ovarian stimulation (COS). GnRH agonist (GnRH-a) triggering is considered an efficient strategy to prevent OHSS in high-risk patient. We performed a review of 11 cases of early and severe OHSS following GnRH-a triggering and freeze all protocol. Electronic databases were searched from inception of each database until October 2021, to identify case reports and case series that reported OHSS after GnRH-a triggering and freeze all approach describing patient demographics, COS protocol and patient outcomes. From the literature review, it is possible to suggest that 1) Following GnRH-a triggering, the risk of early and severe OHSS is not totally cancelled; 2) Despite it is not possible to predict the event, polycystic ovary syndrome is the most common risk factor; 3) the use of GnRH antagonist starting from the day of PU may represent a valid strategy for preventing OHSS in women with high risk profile; 4) Following the unexpected onset of OHSS, measuring serum levels of human chorionic gonadotropin (hCG) is helpful to exclude an inadvertent exogenous administration or a pregnancy. In conclusion, the statement that OHSS risk is eliminated when GnRH-a triggering, a freeze all strategy and no hCG in the luteal phase may generate the idea that this event cannot occur. Although rare, these cases have been observed in a relatively short period of time.