Hysteroscopic surgery is a common gynecological procedure for treating endometrial polyps (EP), which might result in uterine bleeding, infertility [1, 2, 3], and even malignant transformation [4]. Furthermore, about 50% of hysteroscopic surgery complications, such as cervical laceration, uterine bleeding, and perforation, occur during cervical penetration [5, 6]. Therefore, preoperative cervix dilation is essential for an uneventful hysteroscopic surgery and fewer surgical complications.

Cervical pretreatment methods include mechanical and pharmaceutical approaches and clinical cervical softening through resorol injection and disposable cervical dilation rod insertion. Also, oral or cervical placement of prostaglandins is commonly used in clinical practice [7, 8]. As a derivative of prostaglandin E1, misoprostol can degrade cervical collagen fibers, release collagenase and elastase, and soften the cervix through prostaglandin receptors [9]. However, previous studies have shown that misoprostol pretreatment can cause uterine bleeding, vomiting, lower abdominal swelling, abdominal pain, diarrhea, and other adverse events [10, 11]. Due to the relatively widespread side effects, patients with liver or kidney diseases, hypertension, glaucoma, and asthma are not advised to use misoprostol [12].

Recently, antispasmodics, such as phloroglucinol, drotaverine hydrochloride, and rociverine, have been extensively studied in labor induction. Phloroglucinol injection can directly act on the muscle and connective tissue of the cervical tube, thus relaxing and softening the cervix without affecting the uterine physiological contraction, which is partly due to its inhibition of catechol-O-methyltransferase [13]. Moreover, no obvious contraindications have been reported using phloroglucinol as a pretreatment for hysteroscopic surgery. Notable adverse reactions include nausea and dizziness, which were reported to disappear soon after dose reduction or drug withdrawal [14]. Dilapan-S (Minkai Medical Technology Company), a hygroscopic cervical expansion rod specially developed for obstetrics and gynecology, was introduced in China in 2017 [15]. It is made of polymer biomaterials (polypropylene transparent hydrolysis products), with wet volume gradually expanding 3–4 times, whose effect on dilation is achieved by mechanical irritation of the cervix, without any active ingredients [16]. As recent comparative data on mechanical and medical approaches for cervical dilation are inconclusive, more studies are needed to further improve the safety of hysteroscopy for endometrial polyps.

Therefore, this study aimed to compare the effects of Dilapan-S versus phloroglucinol on cervical dilation before the operative hysteroscopy for endometrial polyps. In addition, non-inferiority design was applied to verify whether the clinical application effect on cervical dilation before hysteroscopy was comparable between the two methods.

Among a total of 105 patients enrolled in this study, 55 received phloroglucinol, and 50 received Dilapan-S for cervical dilatation (Table 1). The participants in the phloroglucinol group were 38.20 $\pm$ 7.83 years old with a body mass index (BMI) of 21.85 $\pm$ 3.17 kg/m${}^2$ vs. 38.96 $\pm$ 7.11 years and 22.60 $\pm$ 3.50 kg/m${}^2$ in phloroglucinol group. There were no significant differences in age, BMI, history of vaginal delivery, hysteroscopic electrotomy, and cervical conization between the two groups (all p $>$ 0.05) (Table 1).

The cervical dilation time was shorter in the Dilapan-S group than in the phloroglucinol group (41.74 $\pm$ 8.68 s vs. 62.04 $\pm$ 9.55 s, difference 20.35 s, 95% confidence interval [CI]: 16.84–23.86 s, non-inferiority; p 0.001). Also, more patients achieved highly effective cervical softening in the Dilapan-S group than in the phloroglucinol group (44/50 vs. 1/55, p 0.001) (Table 2).

All the Dilapan-S rods were removed intact. There were 4 cases of diarrhea (p = 0.103), 12 cases of vaginal bleeding (p 0.001), and 4 cases of abdominal pain in the Dilapan-S group (p = 0.283), all of which resolved spontaneously within 24 hours. No adverse reactions were observed in the phloroglucinol group. There were 5 cases of intraoperative water leakage in the phloroglucinol group and 8 in the Dilapan-S group (p = 0.283). No patients reported nausea, vomiting, or fever in any of the groups (Table 2).

The results of the present study showed that Dilapan-S could achieve shorter cervical dilation time. Also, more patients presented with highly effective cervical softening in the Dilapan-S group than in the phloroglucinol group. To the best of our knowledge, this is the first study that compared the two cervical dilation methods. Therefore, our results may help to improve safety and shorten the operation time of hysteroscopy, thus achieving better treatment effects.

Recent studies have reported that among different surgical methods used to treat EP, hysteroscopy has the best performance in view of the operation time, success rate, and complications [17, 18, 19]. In addition, a recent review of more than 1000 cases showed that 32% of infertile women had endometrial polyps, where surgical removal of polyps could promote natural pregnancy and improve the success rate of assisted reproduction [20]. Therefore, this study focused on non-menopausal patients who underwent the hysteroscopic resection of endometrial polyps. These patients all needed cervical dilation before surgery. We did not prescribe antibiotic prophylaxis prior to operative hysteroscopy, which was consistent with existing literature [21].

After Dilapan-S was approved by the US Food and Drug Administration (FDA) in 2015, several studies have compared its effect with traditional labor induction methods [22, 23]. It was found that the application of Dilapan-S could gradually dilate and soften the cervix and initiate endogenous prostaglandin release, causing collagen degradation [24, 25]. In this study, the application of phloroglucinol and Dilapan-S led to successful dilation in all patients, indicating that these two methods could effectively dilate the cervix. The cervical dilation time in the Dilapan-S group was 41.74 $\pm$ 8.68 s. Also, more patients achieved highly effective cervical softening in the Dilapan-S group than in the phloroglucinol group. These results are consistent with previous studies by Crosby et al. [26] and Baev et al. [27], reporting that the dilation time achieved by Dilapan-S was shorter than misoprostol in the comparable population. Therefore, the application of Dilapan-S might have a more prominent effect on cervical dilation than phloroglucinol.

It is important to note that more patients presented with diarrhea, vaginal bleeding, and abdominal pain in Dilapan-S than in the phloroglucinol group. Diarrhea is related to Dilapan-S stimulation of the rectum and anus. Vaginal bleeding may be related to Dilapan-S direct stimulation of the vagina and cervix. Abdominal pain is related to Dilapan-S stimulation of the vaginal sphincter and rectal contraction.Previous studies also noted these adverse events, which appeared to be caused by uterine contraction [28]. Moreover, the efficacy of the medication-based methods is uncertain, as drug absorption is decisive in causing excessive cervical dilation, which affects the surgical field, or results in insufficient dilation that increases the operation time and may lead to cervical trauma bleeding [29, 30]. Although misoprostol was found to have some efficacy in office hysteroscopy compared to placebo [31], it was contraindicated for people with cardiovascular disease, glaucoma, gastrointestinal disorders, asthma, and allergies [7, 14]. No adverse events such as nausea, vomiting, or fever were reported in this study in the two groups. Since 10 mm of dilation is sufficient for hysteroscopic electrotonic surgery, the placement time could be shortened, which might reduce abdominal pain, vaginal bleeding, diarrhea, and other side effects. Moreover, Dilapan-S could be applied in patients with a scarred uterus, as 4 mm rods swell up to 15 mm in 12–24 hours [32].

The present study has some limitations. Due to a relatively small sample size, observing all adverse effects was impossible. The present study was conducted in a single center, which may have led to the low variability in management and may therefore be less applicable to other centers. No uterine and cervical length and width were measured before dilation or surgery. Future multicenter studies with expanded sample sizes are needed to further investigate safety concerns.

Dilapan-S is found to be equally effective for cervical dilation as phloroglucinol; however, it is associated with a higher incidence of vaginal bleeding, diarrhea and abdominal pain complications. We advocate other large-scale studies here.

The data that support the findings of this study are available on request from the corresponding author.

ZL and YX carried out the studies, participated in collecting data, and drafted the manuscript. AL and ZL performed the statistical analysis and participated in its design. AL drafted the manuscript and revised it critically for important intellectual content. All authors read and approved the final manuscript.

This work has been carried out in accordance with the Declaration of Helsinki (2000) of the World Medical Association. The study protocol was approved by the Ethics Committee of Department of Huazhong University of Science and Technology Union Shenzhen Hospital (NO. KY-2021-042-01). All patients signed informed consent forms before they were performed surgery.

We would like to express our gratitude to all those who helped us during the writing of this manuscript. We also wish to thank all the peer reviewers for their opinions and suggestions. It is their selflessness that helped us to successfully complete this paper.

This study was supported by the Shenzhen Science creation Committee (No. JCYJ20190809104403566).

The authors declare no conflict of interest.