The effect of misoprostol on the removal of endometrial polyps: A pilot clinical trial

Abstract Background Endometrial polyps are one of the most common gynecological disorders with a high frequency among infertile women. Hysteroscopic polypectomy remains the gold standard for the treatment of endometrial polyps. As alternative treatments, few drugs have been evaluated to date. Objective To investigate the possible effect of misoprostol on the elimination of endometrial polyps. Materials and Methods In this clinical trial we examined 30 infertile women whose endometrial polyps were confirmed by transvaginal ultrasound with saline injection. All women were administered 400 mg of misoprostol: 200 mg orally and 200 vaginally. 8 hr later, sonography with saline injection was performed again and all women were examined for the presence or absence of endometrial polyps. Finally, the diagnosis was confirmed for all women using hysteroscopy. The main outcome of this study was the elimination of endometrial polyps after misoprostol administration. Results The average size of the endometrial polyps was 14.33 ± 4.26 mm, with a range of 7-22 mm. After misoprostol administration, in 12 out of the 30 women who had shown endometrial polyps in the initial examination, no polyp was found. At follow-up it was found that the smallest endometrial polyp that had been eliminated was 8 mm and the largest was 22 mm. Conclusion The findings of our study revealed that misoprostol can remove up to 40% of endometrial polyps. This drug has the potential to be used as a safe and low-cost first-line treatment before performing hysteroscopic polypectomy.


Introduction
Uterine polyps are one of the most common gynecological disorders and they often present as abnormal uterine bleeding (1). Endometrial polyps are caused by the abnormal growth of glands, stroma or blood vessels, and they protrude from the surface of the endometrium into the uterine cavity (2,3). Risk factors for endometrial polyps include aging, obesity, hypertension, and the use of tamoxifen (4,5). In clinics, their prevalence is estimated to be 7.8-34.9% but they are even more common in infertile women (3,6). Moreover, an increase in the pregnancy rate of 23-65% has been reported after polypectomy (7-9). The molecular mechanism of how the polyps trigger infertility is related to a disturbance in endometrial receptivity (10,11).
On transvaginal ultrasounds, endometrial polyps are seen as hyperechoic areas with a regular environment surrounded by a thin hyperechoic halo inside the uterine cavity (12). Studies have shown that the addition of the vascular Doppler augments the capacity of the vaginal ultrasound in the diagnosis of endometrial polyps (13). Observation of a single feeding vessel in Doppler color flow ultrasound is a typical view of endometrial polyps (14). Indeed, ultrasound with saline injection, when accompanied by the sight of this single feeding vessel, is known to be a key method in the diagnosis of endometrial polyps in premenopausal women (15). Some researchers have considered negative results of sonohysterography as being sufficient in ruling out intrauterine anomalies (16). Nevertheless, other studies have reported that saline infusion sonohysterography (SIS) and hysteroscopy are not significantly different in their effectiveness in diagnosing endometrial polyps (17)(18)(19).
Regarding endometrial polyp treatment, hysteroscopic polypectomy remains the gold standard for endometrial polyp removal (13,20,21). However, hysteroscopic polypectomy commonly results in complications such as infection, hemorrhage, pelvic inflammatory diseases, uterine rupture or cervical injury, and the need for the use of gas or fluid to dilate the uterus should also be taken into account (2). Only a few alternative treatments have been studied so far, including the use of the intrauterine device producing Levonorgestrol, oral contraceptives, and gonadotropin-releasing hormone (22)(23)(24).
At Yazd Reproductive Sciences Institute, we routinely use misoprostol (Cytotec, 200 Mcg, Pfizer, Germany) to prepare the cervix before hysteroscopic polypectomy in infertile women for whom endometrial polyps have been detected on vaginal ultrasound. Interestingly, we have noticed that in these cases there have been no signs of the polyps when the women underwent hysteroscopic polypectomy. Therefore, we aimed to investigate the possible effect of misoprostol on the elimination of endometrial polyps.

Materials and Methods
In this pilot clinical trial conducted from July to November 2020 at the Yazd Reproductive Sciences Institute, Yazd, Iran 30 infertile women aged 18-45 yr were studied. Infertility was defined as the inability to achieve pregnancy after 1 yr of regular intercourse without using any contraceptives (1). The presence of endometrial polyps was confirmed in all women by sonography with saline injection. Transvaginal ultrasound with color Doppler (TVCD) needed to be performed in some cases. Women with untreated uterine malformations, pelvic inflammatory diseases, or a history of sensitivity to prostaglandin analogues were excluded from the research. The process of ultrasound with saline injection, misoprostol, and finally, hysteroscopy were fully explained to all of the women. The Netherlands) was performed for some cases by an experienced and trained physician to confirm the diagnosis. The endometrial polyp was defined as a localized hyper echo lesion in color Doppler characterized by a smooth and well-defined border with a feeding vessel.
If the endometrial polyp was confirmed at this stage, the size of the polyp was also determined and the women's characteristics including age, body mass index (BMI), and the type of infertility, being either primary or secondary, were

Results
Initially, 34 women were enrolled in the study.  (Table I)

Discussion
As far as we know, our study is the first to investigate the effect of misoprostol on the removal of endometrial polyps in infertile women.
In our study, misoprostol had a therapeutic effect on 40% of polyps in triggering their removal from the uterus.
Misoprostol is a synthetic analogue of prostaglandin E1, which has several applications in obstetrics and gynecology (25).

Conclusion
In conclusion, the findings of our study revealed that misoprostol can remove up to 40% of endometrial polyps. This drug has the potential to be used as a safe and low-cost first-line treatment before performing hysteroscopic polypectomy.