Study question: Does intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) prevent adhesion reformation and promote endometrial growth after hysteroscopic adhesiolysis?
Summary answer: Intrauterine perfusion of G-CSF can increase endometrial thickness but does not prevent the recurrence of intrauterine adhesions (IUAs) in patients with Asherman syndrome (AS) after surgery.
What is known already: Intrauterine infusion of G-CSF has been used in attempts to treat patients with recurrent miscarriage and an idiopathic thin endometrium for either fresh or frozen-thawed embryo transfer cycles but without uniform efficacy. There have been no reports on the effect of G-CSF on the recurrence of IUAs, endometrial regrowth or pregnancy results in specific populations with AS.
Study design, size, duration: This two-center prospective double-blind randomized controlled trial ran between April 2016 and August 2021. In it, 245 patients with moderate to severe AS were randomized to G-CSF and control groups at a 1:1 ratio; 229 women were included in the adhesion recurrence analysis; and 164 patients were analyzed for pregnancy outcomes.
Participants/materials, setting, methods: All eligible patients received the first hysteroscopic adhesion separation and balloon placement procedure. Patients who met our inclusion and exclusion criteria were randomized after surgery. These patients returned for balloon removal and underwent intrauterine perfusion with 300 µg (1.8 ml) G-CSF or 1.8 ml normal saline according to randomization at 7 days after surgery. A second-look hysteroscopy was carried out 1-2 months later. The primary outcome was the rate of formation of new adhesions at the second hysteroscopy. The secondary outcomes included endometrial thickness in the periovulatory period after surgery, as well as the clinical pregnancy and live birth rates.
Main results and the role of chance: Age, menstrual cycle characteristics, pregnancy history and IUA score before surgery were similar between groups. There were no statistically significant differences in the adhesion reformation rate or median adhesion score reduction. However, G-CSF perfusion significantly improved endometrial thickness (7.91 ± 2.12 mm vs 7.22 ± 2.04 mm; P = 0.019, 95% CI for difference: -1.26 to -0.12), as well as cumulative pregnancy and live birth rate over time (P = 0.017 and P = 0.042). Furthermore, multivariate logistic regression analysis showed that postoperative endometrial thickness was an independent prognostic factor for pregnancy and live birth rates.
Limitations, reasons for caution: These results cannot be extended to older patients or those without AS, as our subjects had moderate or severe AS and were aged <40 years. The low number of patients included in the fertility analysis could lead to biased results.
Wider implications of the findings: Intrauterine perfusion of G-CSF could be an effective adjuvant therapy for patients with AS to increase endometrial thickness.
Study funding/competing interest(s): This study was supported by grants from the National Key Research and Development Program of China (2018YFC1004800), the National Natural Science Foundation of China (82001624 and 81871209), the Natural Science Foundation of Zhejiang Province (LQ20H040004) and the provincial and ministerial construction project of Zhejiang Province (2017 WKJ-ZJ-1721). The authors declare that they have no conflicts of interest regarding this work.
Trial registration number: ClinicalTrials.gov (NCT02855632).
Trial registration date: 4 March 2016.
Date of first patient’s enrolment: 13 April 2016.
Keywords: Asherman syndrome; endometrium; granulocyte colony-stimulating factor; hysteroscopic adhesiolysis; intrauterine adhesion.
© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.