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.
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.
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 (17-19).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
(22-24).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.
2. 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 women underwent SIS in the proliferative phase. 20 min before SIS, 500 mg of oral
azithromycin tablets (Shafa Pharmaceutical & Hygienic Co., Iran) and a diclofenac
suppository of 100 mg (Darou Pakhsh Pharmaceutical Mfg Co., Iran) were used in all the
women, and sonohysterography with an intrauterine injection of 20-25 cc of normal saline
was performed. TVCD (Phillips model Affiniti 70 W, 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 recorded.All women were administered 400 mg of misoprostol (Cytotec, 200 Mcg, Pfizer, Germany),
200 mg orally and 200 vaginally, 48 hr after the confirmation of endometrial polyp
diagnosis. 8 hr later, all women were examined for the presence or absence of
endometrial polyps. Finally, all women underwent hysteroscopy for confirmation of the
diagnosis and an endometrial biopsy was taken. Moreover, in the 18 cases in which
endometrial polyps remained after misoprostol administration, polypectomy was performed
through a resectoscope.
Ethical considerations
All of the women were fully explained about process of ultrasound with saline
injection, misoprostol, and finally hysteroscopy. They all signed the informed
consent form. The study protocol was approved by the Ethics Committee of Yazd
Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences,
Yazd, Iran (Code: IR.SSU.RSI.REC.1399.010).
3. Results
Initially, 34 women were enrolled in the study. 3 of these women did not meet the
inclusion criteria. Therefore, 31 women were assessed for endometrial polyps through SIS
and in some cases SIS plus TVCD. 1 woman was excluded from the study due to a diagnosis
of submucosal myoma. Finally, 30 women with a diagnosis of endometrial polyps received
misoprostol (Figure 1). The demographic and clinical features of all of the participants
are listed in table I. The mean age of the women was 34.00
4.79 yr and their mean BMI was 27.31
3.74. In total, 23 women (76.7%) had a BMI
25, 17 women (56.7%) had secondary infertility and 13 (43.3%) reported
a history of abortion. The average size of the endometrial polyps was 14.33
4.26 mm, the smallest of which was 7 mm and the largest was 22 mm
(Table I).After misoprostol administration, in 12 out of the 30 women who had shown endometrial
polyps in the initial examination, no polyp was found; this was identified through both
SIS follow-up and hysteroscopy. At the follow-up it was found that the smallest
endometrial polyp that had been eliminated was 8 mm and the largest was 22 mm. There was
no statistically significant correlation between the polyp size and polyp elimination
after misoprostol administration (p = 0.87). As is shown in figure 2, 41.7% of the
endometrial polyps larger than 15 mm and 38.9% of those
15 mm were eliminated after misoprostol administration. No serious
side effects for misoprostol were reported except for pelvic pain in some cases. The
most common abnormal pathology associated with the endometrial polyps was proliferative
disorder which was observed in 5 cases (35.0%), and 1 case (3.3%) showed an atypical
myofibromatous polyp. In addition, all of the results obtained in the follow-up of the
patients by the SIS and TVCD methods in terms of the presence or absence of endometrial
polyps were consistent with the hysteroscopy results.The mean and standard deviation of participants' age, BMI and polyp size (n =
30)Flow-chart of the endometrial polyp diagnosis and treatment, TVCD: Transvaginal
color doppler, SIS: Saline infusion sonohysterography.Endometrial polyp removal rate based on the polyp size.
4. 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). The advantage of misoprostol over other prostaglandin
analogues is its long half-life, availability, lack of a need for refrigeration, and low
cost (26). In our study, a dose of 400 micrograms of misoprostol was used, which is
widely deployed in obstetric patients, and no serious side effects have been reported
with this dose (27). In addition, studies have demonstrated that doses of 200, 400 and
1000 mg of misoprostol taken vaginally or orally 9-12 hr before hysteroscopy are
effective in dilating the cervix in premenopausal women (28-30).Wada-Hiraike and colleagues examined the effect of oral contraceptive pills on the
removal of uterine polyps and concluded that stalkless polyps respond better to oral
contraceptives than stalked polyps (24). Moreover, Chowdary and colleagues reported the
beneficial effect of the intrauterine device Mirena in eliminating polyps in
premenopausal women with heavy menstrual bleeding (31). However, based on the 2
mentioned studies, the treatment of polyps lasted an average of 80-90 days, and the use
of these drugs for several months is hardly welcomed by infertile patients. Vercellini
et al. displayed the beneficial effect of gonadotropin-releasing hormone agonist as an
adjuvant polyp treatment before hysteroscopic resection; however, the common use of this
drug is not appealing due to its side effects and cost (23).One of the strengths of our study was its prospective aspect that applied a combination
of several early diagnostic methods to confirm uterine polyps so as to minimize
diagnostic error. In this study, all ultrasounds, including TVCD and SIS, were performed
by a qualified physician to minimize the potential effect of operator error.
Sensitivity, specificity, positive predictive value, and negative predictive value of
vaginal ultrasound in the diagnosis of endometrial polyps have been shown to be 86%,
94%, 91% and 90%, respectively (32). Using TVCD, the sensitivity increases up to 97%
(33). Although hysteroscopy and guided biopsy are standard diagnostic methods for
endometrial polyps, they are invasive procedures and are hence unlikely suitable to be
repeated at short intervals of time (1). Therefore, in order to better confirm
endometrial polyps, in addition to ultrasound with saline injection as a safe procedure,
we used TVCD which has been demonstrated as equally effective as hysteroscopy in several
studies (17, 18).In various studies, SIS, compared with hysteroscopy, has been identified as having a
sensitivity of 58-100%, a specificity of 35-100%, a positive p-value of 70-100%, and a
negative p-value of 83-100% (17, 34-37). Furthermore, because our patients were
infertile, deploying SIS as a diagnostic method could not only confirm the presence of
the polyp but also provide the possibility to examine the fallopian tubes for openness
and evaluate the uterine cavity and other structures inside the pelvis (12, 18). Another
strength of our study was that time was not wasted on unnecessarily providing the
standard treatment for polyps (hysteroscopic polypectomy) for infertile women, and the
women could also receive other appropriate infertility treatments as soon as possible
after diagnosis. The main weakness of this study was the lack of a control group.Celik et al. investigated the effect of misoprostol on uterine blood flow in patients
with uterine myoma and observed a reduction in uterine artery blood flow following
misoprostol administration. They proposed that vasoconstriction, and thus contraction of
uterine muscles, could explain this effect of misoprostol. They suggested that
misoprostol can likely be regarded as a treatment option for uterine myoma in the future
(27). In our study, misoprostol could eliminate 40% of the endometrial polyps; however,
our results showed that there was no statistically significant association between the
polyp size and polyp removal. It has previously been indicated that endometrial polyps
larger than 15 mm may be less likely to display spontaneous regression, and that
polypectomy should be considered for symptomatic patients (3, 38). Nonetheless, in the
current study, a high percentage of polyps larger than 15 mm (41.7%) were resolved by
misoprostol without polypectomy. The vasoconstrictor effect of the drug on the artery
feeding the polyp and thus the formation of uterine contractions might have triggered
the polyp to be eliminated from the surface of the endometrium.Our study was the first to investigate the effect of misoprostol on the removal of
endometrial polyps. Further studies are thus recommended which include a control group
and employ repeated high doses of this drug, to investigate its possible further
efficacy and to see if it can be considered as a safe, low-cost, and first-line
treatment alternative for uterine polyps.
5. 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.
Conflict of Interest
The authors declare that there is no conflict of interest.
Table 1
The mean and standard deviation of participants' age, BMI and polyp size (n =
30)