TOPLINE:

Inhaled nitrous oxide (N₂O) significantly reduced pain during office hysteroscopy compared with ambient air, with intraprocedural pain scores more than 40% lower in the N₂O group than in the ambient air group. The analgesic effect is particularly pronounced in postmenopausal women, who also experience reduced pain at uterine entry, along with higher procedure completion rates and greater patient satisfaction.

METHODOLOGY:

• A total of 214 women undergoing office hysteroscopy at a university-affiliated hospital in Israel were randomly assigned in a 1:1 ratio to receive either inhaled N2O (n = 110) or ambient air (n = 104) through a self-administered face mask between July and November 2025.
• Participants inhaled either a fixed 50:50 N2O/oxygen mixture or ambient air for 1 minute before the procedure and continued inhalation throughout, with procedures performed using a vaginoscopic approach by three experienced hysteroscopists.
• Pain was assessed using a 10-point visual analog scale (VAS) at three timepoints: uterine entry, during the procedure, and immediately after completion, with 0 representing no pain and 10 representing the worst imaginable pain.
• The primary outcome was the difference in VAS scores between groups during procedural stages, and secondary outcomes included adverse events, procedure completion rate, and patient satisfaction defined as willingness to repeat the procedure with the same inhaled agent.
• Prespecified subgroup analyses evaluated whether nulliparity, prior cesarean delivery, procedure duration, and menopausal status were associated with greater benefit from N2O.

TAKEAWAY:

• Intraprocedural pain was significantly lower in the N2O group than in the ambient air group (2.23 ± 3.29 vs 3.96 ± 3.31; P < .001), with repeated-measures analysis of variance demonstrating a significant group × procedural stage interaction (P = .002).
• Among postmenopausal women, N2O significantly reduced pain both at uterine entry (5.47 ± 3.38 vs 8.00 ± 2.72; P = .013) and during the procedure (2.42 ± 3.86 vs 6.56 ± 2.79; P = .002), with the analgesic effect more pronounced than that in premenopausal participants.
• Procedure completion rates were significantly higher in the N2O group (93.6% vs 83.7%; P = .021), and patient satisfaction was significantly greater (80.9% vs 47.1%; P < .001).
• Presyncope occurred significantly more frequently in the ambient air group than in the N2O group (11.5% vs 2.7%; P = .012), likely reflecting vasovagal response to unrelieved pain, whereas overall adverse event rates were comparable between groups.

IN PRACTICE:

“Inhaled N₂O significantly reduces intraprocedural pain during office operative hysteroscopy, improves patient satisfaction, and increases procedure completion rates, all with a low incidence of mild, self-limited adverse effects.… Our findings support consideration of N₂O as an analgesic option in office-based hysteroscopic practice to enhance both patient experience and procedural success,” authors of the study wrote.

SOURCE:

The study was led by Sabina Razdolsky, MD, and Rina Yaniv-Tamir, MD, Department of Obstetrics and Gynecology, Mayanei Hayeshua Medical Center, Bnei Brak, affiliated with Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. It was published online in Obstetrics & Gynecology.

LIMITATIONS:

This was a single-center study with a relatively demographically homogeneous population, and the cohort included fewer nulliparous and more multiparous women. Race and ethnicity data were not systematically collected, and the proportion of postmenopausal women was relatively small, reflecting the clinical case mix of the ambulatory practice. Therefore, the findings may not be fully generalizable to populations with different demographic or reproductive characteristics. Although the postmenopausal subgroup was relatively small and underpowered, the analgesic effect of N₂O remained statistically significant; thus, the main limitation concerns generalizability rather than the internal validity of the finding in postmenopausal women. Although intention-to-treat analysis minimized bias, the discontinuation of the procedure due to pain in approximately 10% of participants led to unblinding. Additionally, the lack of N₂O effect at uterine entry may be related to insufficient duration of preinhalation time.

DISCLOSURES:

No relevant conflicts of interest or potential conflicts were reported by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.