Septum Resection Versus Expectant Management in Women With a Septate Uterus: An International Multicentre Open-Label Randomized Controlled Trial

Septate uterus, a congenital uterine anomaly, affects approximately 0.2% to 2.3% of women of reproductive age and is associated with increased risk of subfertility, pregnancy loss, and preterm birth. The standard treatment for septate uterus is hysteroscopic septum resection, although various obstetric and gynecologic academic societies differ in their support of the procedure, often citing inadequate evidence of effectiveness for a reason to avoid surgery. This international, multicenter, open-label randomized controlled trial aimed to compare reproductive outcomes in women with a septate uterus after hysteroscopic septum resection versus expectant management. Three tertiary-care and 4 secondarycare hospitals in the Netherlands as well as 3 tertiary care hospitals in the United States, United Kingdom, and Iran, respectively, were study sites. To be eligible, women must have had a septate uterus, desired pregnancy, and had a history of subfertility, pregnancy loss, or preterm birth. Participants were randomly allocated in a 1:1 ratio to hysteroscopic septum resection or expectant management. Participants randomized to expectant management received no specific interventions and were advised to continue attempting to conceive naturally or with assisted reproductive technologies. Participants in the control group were given the option to opt for hysteroscopic septum resection in the event of the first pregnancy after randomization resulting in pregnancy loss or if pregnancy did not occur after 1 year of follow-up. The primary study outcome was conception leading to live birth within 1 year of randomization. Participants were followed for at least 1 year and those that conceived were followed for the course of the pregnancy. An intention-to-treat analysis was performed, and Kaplan-Meier curves using the log-rank test were constructed to compare the treatment arms and corresponding hazard rates with 95% confidence intervals. A total of 80 participants were randomized (40 in septum resection, 40 in expectant management), with 79 included in the intention-to-treat analysis (39 in septum resection, 40 in expectant management) and 69 included in the per-protocol analysis (36 in septum resection, 33 in expectant management). The intention-to-treat analysis revealed a 31% live birth rate among those receiving a septum resection compared with a 35% live birth rate with expectant management (relative risk, 0.88; 95% confidence interval [CI], 0.47-1.7; absolute risk difference, -4.2%; 95% CI, -24.9% to 16.5%). No significant differences were observed regarding clinical pregnancy rate, ongoing pregnancy rate, pregnancy loss, or preterm birth rates between the groups. The average length of time to conception leading to live birth from randomization was 9.8 months (95% CI, 8.6-11) for septum resection and 9.2 months (95% CI, 7.8-11) for expectant management (log rank P = 0.64) (hazards ratio, 0.83; 95% CI, 0.39-1.9). The per-protocol analysis likewise showed no evidence of a difference in reproductive outcomes between the 2 groups. The results of this study find that septum resection did not improve live birth rate compared with expectant management among women with a septate uterus desiring pregnancy.