Outpatient paracentesis for Ovarian Hyperstimulation Syndrome: STOP-OHSS feasibility study and RCT Synopsis.

Background: Ovarian hyperstimulation syndrome is a potentially serious complication of fertility treatments. Standard care often involves monitoring, then hospitalisation for severe cases. Some evidence suggests early outpatient paracentesis may prevent hospitalisation, but adequately powered randomised trials are lacking. Objectives: To establish the clinical and cost-effectiveness, safety and acceptability of early active outpatient management for moderate or severe ovarian hyperstimulation syndrome. Design and methods: A pragmatic, parallel, open-label, multicentre, superiority, adaptive, group sequential randomised controlled trial with an internal pilot was planned. The study included preliminary qualitative work and a post-trial survey. The main trial recruited participants with moderate or severe, early or late ovarian hyperstimulation syndrome from UK fertility clinics. Participants were randomised 1 : 1 to receive either outpatient paracentesis or usual care (conservative management). The primary outcome was ovarian hyperstimulation syndrome-related hospital admission within 28 days. Results: The trial was terminated early due to poor recruitment. Only 8 participants were randomised (5 to conservative management, 3 to outpatient paracentesis) across 3 of 9 opened sites, compared to the planned 224 participants. All eight had moderate ovarian hyperstimulation syndrome at baseline. Two participants were hospitalised for ovarian hyperstimulation syndrome-related reasons (one from each group). Six participants' symptoms resolved during follow-up, while two had unknown outcomes. There were no reported serious adverse events caused by the intervention. The post-trial survey of 16 fertility centres found increased use of preventive measures like freeze-all cycles, antagonist protocols and gonadotropin-releasing hormone trigger, during and after the SARS-CoV-2 (COVID-19) pandemic. Limitations: The small sample size precludes drawing any definitive conclusions about effectiveness, safety or cost-effectiveness. The study was severely impacted by the COVID-19 pandemic, affecting site set-up and recruitment, and changes in clinical practice during the pandemic may have reduced ovarian hyperstimulation syndrome cases. Conclusions: No definitive clinical conclusions can be drawn from this study about the effectiveness of outpatient management compared to conservative management. The pandemic prompted lasting modifications in ovarian hyperstimulation syndrome prevention strategies at many fertility clinics. Future work: Given the observed low incidence rates of ovarian hyperstimulation syndrome and challenges in recruitment, future research may need to consider alternative study designs in observational settings rather than randomised trials that reflect the changing reality of clinical management and prevention of ovarian hyperstimulation syndrome, particularly following the recent COVID pandemic. Additionally, the research community should reflect on strategies to improve trial resilience and adaptability in the face of major disruptions like pandemics. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128137.