Efficacy and safety of nalbuphine vs. pethidine in oocyte retrieval: a non-inferiority, double-blinded, randomized controlled trial

Objective The purpose of this study was to evaluate the efficacy and safety of Nalbuphine compared to Pethidine for pain relief during oocyte retrieval. Methods In a double-blinded, non-inferiority randomized controlled trial ( n = 94), participants were randomized equally into two groups. The intervention group received 10 mg intravenous Nalbuphine combined with 5 mg of Midazolam, while the control group received 50 mg intravenous Pethidine with 5 mg of Midazolam. The primary outcome was pain score measured immediately postoperatively using a visual analogue scale. Secondary outcomes included pain score at 2 and 6 h postoperatively, operator score for patient cooperation, vital signs, number of total oocytes and metaphase II (MII) oocytes retrieved, operative time, recovery time, side effects, and need for rescue analgesia. Results Nalbuphine demonstrated non-inferiority to Pethidine for pain control at 0 h postoperatively, with a mean difference of 0.52 (95% CI: −0.40 to 1.44). Similar findings were observed at 2 h (mean difference −0.46; 95% CI: −1.30 to 0.38), while at 6 h Nalbuphine showed significantly lower pain scores (mean difference −1.28; 95% CI: −2.15 to −0.41). No significant differences were observed between groups in operator score, recovery time, or rescue analgesia requirements. The number and quality of oocytes retrieved were not affected by the analgesic regimen. Side effects such as nausea, vomiting, dizziness, and tachycardia were compared and showed no significant differences. Conclusion Nalbuphine demonstrated non-inferior analgesia to Pethidine for oocyte retrieval with a favorable safety profile. Its impact on long-term reproductive outcomes and clinical superiority warrants further investigation. Clinical Trial Registration https://www.thaiclinicaltrials.org/show/TCTR20240406003 , identifier TCTR20240406003.