Is there a difference in ovarian hyperstimulation syndrome rates in freeze-all treatment cycles in high-risk patients treated with different GnRH agonist triggers?

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted reproductive technology (ART). Risk factors for OHSS include female age, polycystic ovarian morphology and high ovarian reserve. The use of a gonadotrophin-releasing hormone (GnRH) agonist trigger in a freeze-all cycle is an effective strategy for reducing the risk of OHSS in suspected high responders. Various GnRH agonist trigger preparations exist but their use is subject to manufacturer availability. The national shortage of Buserelin necessitated a switch to alternative GnRH agonist trigger preparations such as Modified-Release (MR) Triptorelin resulting in a spike in OHSS cases, prompting an urgent review of our local treatment protocols and an immediate switch to Nafarelin (nasal preparation). We performed a retrospective study of freeze-all GnRH antagonist treatment cycles treated with a GnRH agonist (Triptorelin-MR, Nafarelin, and Buserelin) trigger at a London fertility clinic. The high-risk cohort consisted of patients with ≥18 follicles >12mm on ultrasonography. The diagnosis of OHSS was based on the criteria outlined by the Royal College of Obstetricians and Gynaecologists (RCOG). Relevant clinical data were extracted from medical records including female age, antral follicle count (AFC), anti-Mullerian hormone (AMH), ovarian stimulation dose (international units; IU), trigger preparation, oestradiol level on trigger day (pmol/l), oocyte yield, and the diagnosis and management of OHSS. A total of 333 patients underwent a freeze-all GnRH antagonist cycle between January 2023 and September 2024, 224 due to a high-risk of OHSS (≥18 follicles >12mm). The GnRH agonist preparations used included: Triptorelin-MR only (0.75 mg subcutaneous injection, SC; n = 69), Triptorelin-MR (0.375 mg SC) plus Menopur (150 IU SC; n = 49), Buserelin (2 mg SC; n = 69), and Nafarelin (1.6 mg nasal spray; n = 37). Forty-three patients met the RCOG diagnostic criteria for OHSS (mild n = 5, moderate n = 25 and severe n = 13). Six patients required inpatient OHSS management; none required intensive care or a chest/abdominal drain. Of those that developed severe OHSS, 92.3% (n = 12/13) had received Triptorelin-MR only or in combination with Menopur. Based on this cohort, Triptorelin-MR containing triggers are associated with a 12-fold increased risk of severe OHSS compared with other preparations and should not be used as a GnRH agonist trigger in patients at high risk of OHSS.