A randomized double-blinded non-inferiority trial comparing fentanyl and midazolam with pethidine and diazepam for pain relief during oocyte retrieval

Abstract

Research question: Is fentanyl and midazolam non-inferior to pethidine and diazepam in pain relief during oocyte retrieval under conscious sedation? Design: A randomized double-blinded non-inferiority trial of 170 infertile women undergoing oocyte retrieval under conscious sedation in an assisted reproduction centre. The women were randomized to receive intravenously either 0.1 mg fentanyl and 5 mg midazolam or 25 mg pethidine and 5 mg diazepam, plus paracervical block with 10 ml 1% lignocaine. The primary outcome was abdominal pain level during retrieval assessed by linear visual analogue scale from 0–10. Secondary outcomes included vaginal pain levels during and after retrieval and postoperative abdominal pain levels and side-effects, satisfaction level, clinical pregnancy and ongoing pregnancy rates. A pre-defined non-inferiority margin of 1 for the difference in pain levels between two groups was set. Results: Vaginal and abdominal pain levels during retrieval were significantly lower in the fentanyl and midazolam group compared with the pethidine and diazepam group (per-protocol analysis, vaginal pain: 1.6 versus 4.3; mean difference: –2.7, 95% CI –3.7, –1.8; P < 0.001; abdominal pain: 2.9 versus 5.2; mean difference: –2.3, 95% CI –3.3 to –1.3; P < 0.001 for non-inferiority). No differences were observed in these pain levels after retrieval. Most women experienced no postoperative side-effects. The fentanyl and midazolam group had better sedation level, satisfaction level on pain relief and satisfaction on the overall retrieval procedure than the pethidine and diazepam group. No significant differences were found in clinical pregnancy and ongoing pregnancy rates between the two groups. Conclusion: The fentanyl and midazolam group had significantly lower vaginal and abdominal pain levels during oocyte retrieval than the pethidine and diazepam group. © 2020 Reproductive Healthcare Ltd.