Is there a difference in ovarian hyperstimulation syndrome rates in freeze-all treatment cycles in high-risk patients treated with different GnRH agonist triggers?
Triptorelin-MR triggers are associated with a 12-fold increased risk of severe ovarian hyperstimulation syndrome in high-risk patients, suggesting they should be avoided in these cases.
Where it sits
this study against the rest of the hmg (human menopausal gonadotropin) corpusSummary and findings
This study measured the rates of ovarian hyperstimulation syndrome (OHSS) in high-risk patients undergoing freeze-all treatment cycles with different GnRH agonist triggers. A total of 333 patients were included, with 224 classified as high-risk due to ≥18 follicles >12mm. The findings indicated a significant association between the use of Triptorelin-MR and increased rates of severe OHSS.
Abstract
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.
Background
This paper addresses the risk of ovarian hyperstimulation syndrome (OHSS) in patients undergoing assisted reproductive technology (ART), particularly in high-risk populations. Previous studies have identified various risk factors for OHSS, including female age and ovarian reserve. Understanding the impact of different GnRH agonist triggers on OHSS rates is critical for optimizing treatment protocols in high-risk patients.
Methods
This retrospective study analyzed 333 patients who underwent freeze-all GnRH antagonist treatment cycles at a London fertility clinic between January 2023 and September 2024. The high-risk cohort included patients with ≥18 follicles >12mm. The GnRH agonist triggers evaluated included Triptorelin-MR, Buserelin, and Nafarelin, with doses reported as 0.75 mg SC, 2 mg SC, and 1.6 mg nasal spray, respectively. The primary outcome measure was the incidence of OHSS diagnosed according to RCOG criteria.
Results
The primary endpoint revealed that 43 patients met the RCOG diagnostic criteria for OHSS, with a breakdown of mild (n=5), moderate (n=25), and severe (n=13) cases. The study found a 12-fold increased risk of severe OHSS associated with Triptorelin-MR triggers compared to other preparations. Six patients required inpatient management for OHSS, but none required intensive care or invasive procedures.
Interpretation
The findings suggest a significant association between the use of Triptorelin-MR and increased rates of severe OHSS, which aligns with previous literature indicating the risks associated with certain GnRH agonist triggers. However, the clinical significance of a 12-fold increase should be interpreted cautiously, given the retrospective nature of the study and potential confounding factors. The results imply that alternative triggers may be preferable in high-risk populations to mitigate OHSS risk.
Key findings
- 12-fold increased risk of severe OHSS with Triptorelin-MR compared to other preparations.
- 43 patients met the RCOG diagnostic criteria for OHSS (mild n=5, moderate n=25, severe n=13).
- 92.3% (n=12/13) of severe OHSS cases received Triptorelin-MR only or in combination with Menopur.
- Total of 333 patients underwent a freeze-all GnRH antagonist cycle.
- 224 patients were classified as high-risk for OHSS.
Limitations
- retrospective study design
- potential selection bias
- data reliant on medical records
- single-site study
- short follow-up period