Nitrous Oxide for Pain Management in Office Hysteroscopy: A Randomized Placebo-Controlled Trial

To assess pain during office operative hysteroscopy with or without inhaled nitrous oxide (N 2 O).

A prospective, randomized, double-blind, placebo-controlled trial was conducted at a single university-affiliated tertiary care hospital. Women undergoing office operative hysteroscopy were randomized in 1:1 ratio to receive either inhaled N 2 O or ambient air through a self-administered face mask. Pain was assessed using a 10-point visual analog scale at three timepoints: uterine entry, during the procedure, and postprocedure.

Between July and November 2025, a total of 214 women were randomized to receive either N 2 O (n=110) or ambient air (n=104). Baseline demographics and procedural characteristics were comparable between groups. Intraprocedural pain was significantly lower in the N 2 O group (2.23±3.29 vs 3.96±3.31, P <.001). Among postmenopausal women, the analgesic effect of N 2 O was more pronounced, with significantly lower 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). Procedure completion rates were higher in the N 2 O group (93.6% vs 83.7%, P =.021), and patient satisfaction was significantly greater (80.9% vs 47.1%, P <.001).

Inhaled N 2 O significantly reduces pain during office operative hysteroscopy, improves patient satisfaction, and decreases the rate of incomplete procedures, with a low incidence of adverse events. These findings support its use as an effective and well-tolerated analgesic option for outpatient hysteroscopic procedures.

ClinicalTrials.gov, NCT07074795.