1 Obstetrics and Gynaecology, Reproductive and Developmental Sciences, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh, EH3 9EW, 2 Obstetrics and Gynaecology, Dumfries and Galloway Royal Infirmary, Dumfries and 3 Department of Pathology, Medical School, Teviot Place, Edinburgh, EH8 9AG, UK
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Abstract |
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Key words: intrauterine polyps/hysteroscopy/levonorgestrel/saline infusion sonography
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Introduction |
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Case reports |
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Case 3
A 67-year-old parous patient presented with recurrent postmenopausal bleeding, having had a menopause at the age of 42. She had a hysteroscopy, which showed a normal uterine cavity, and endometrial biopsies that consistently showed simple cystic hyperplasia. A consensus view from local gynaecological oncologists and pathologists advised high-dose progestogen therapy in order to avoid surgical management, if possible, in view of the patient's extensive past surgical history, which included a Hartmann's procedure. An LNG-IUS was inserted but bleeding did not settle despite endometrial biopsy showing pseudo-decidualization. In view of this, 3 months after insertion of the LNG-IUS a transvaginal ultrasound scan was performed, which demonstrated what appeared to be a thickened endometrium (22 mm) with a cystic appearance (Figure 2). In order to clarify the nature of the endometrial abnormality, saline infusion sonography (SIS) was performed. This technique involved the instillation of a small amount (5 ml) of sterile saline into the uterine cavity through a 5-Foley paediatric catheter (or hysterosalpingography or insemination catheter), followed by transvaginal ultrasound. As seen in the scan photographs (Figure 3
), the anechoic saline distended the uterine cavity and clearly delineated an intracavity polyp, thus demonstrating that the endometrial lining was normal and that the apparent thickened endometrium, which had been observed with plain vaginal ultrasound, was the result of the polyp. Admission was arranged for in-patient hysteroscopy and polypectomy. Again pathology showed simple cystic hyperplasia within the endometrial polyp with surrounding endometrium showing pseudo-decidualization of the stroma and glandular atrophy. (Figure 4
) She remained bleed free after the removal of this polyp and an outpatient hysteroscopy 6 months later showed an atrophic but otherwise normal uterine cavity with the LNG-IUS in situ. Currently the patient is bleed free, and biopsy is to be conducted only if bleeding recurs.
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Discussion |
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Mechanisms responsible for the development of an endometrial polyp on the background of endometrial gland atrophy are unclear. Micropolyps have been described within the endometrium after a mean duration of use of 48 months (Silverberg et al., 1986). This finding, however, has not been confirmed by other groups who looked at endometrium up to 12 months after insertion of the intrauterine system (Critchley et al., 1998a
). Changes within the endometrium, which resemble first-trimester decidua, with LNG-IUS use, were demonstrated. There was elevation of granulocytemacrophage colony-stimulating factor (GM-CSF) and an increase in CD56+ large granular lymphocytes (LGL) seen with the pseudo-decidualization associated with the LNG-IUS as is seen in normal first-trimester decidua. However, bleeding seen with progestogen-only contraceptives is not commonly encountered in the first trimester of a healthy continuing pregnancy. Progesterone receptors (PR), mainly the PRB subtype, are down-regulated in the stroma of LNG-IUS users (Critchley et al., 1998b
). A down-regulation of PR may result in the endometrium being less responsive to progestin-mediated events. Other factors may also be involved in breakthrough bleeding which may explain some of the underlying mechanisms. Metalloproteinase-9 (MMP-9) is an enzyme capable of degrading basement membrane. MMP-9 positive cells, neutrophils and eosinophils have been shown to be significantly increased in endometrial biopsies taken from users of the progestogen only implant, displaying a shedding morphology and in normal controls at menstruation (Vincent et al., 1999
). This would suggest that MMP-9 may be involved in breakthrough bleeding in women.
Although not commonly used as a treatment for endometrial hyperplasia, the LNG-IUS used in this case produced a pseudo-decidualized endometrium with glandular atrophy, although hyperplasia persisted within the polyp itself. The use of an LNG-IUS releasing only 3 µg of levonorgestrel each day, has been used in women with histologically confirmed endometrial hyperplasia of all types (Perino et al., 1987). In 93% of cases the typical decidual reaction seen with LNG-IUS was evident without hyperplasia. In one case, of adenomatous hyperplasia with atypia, there was decidualization of the stroma but with persistent hyperplasia. The use of the 20 µg-releasing LNG-IUS was found to be associated with regression of hyperplasia, regardless of pattern, to an endometrium showing glandular atrophy and pseudo-decidualization (Scarselli et al., 1988
)
Studies using SIS have established that it has an accuracy for detecting uterine cavity abnormalities at least equivalent to that of hysteroscopy (Goldstein, 1994; O'Connell et al., 1998
). The advantages of SIS include the widely available inexpensive equipment, detection of uterine, adnexal and other pelvic abnormalities, and good performance in bleeding uteri.
Out-patient hysteroscopy and saline infusion scanning are warranted investigations in women who develop new symptoms of bleeding after a period of amenorrhoea, or who continue to complain of persistent heavy bleeding with an LNG-IUS in situ. Co-existing intrauterine pathology, such as endometrial polyps, can be excluded before considering removing the levonorgestrel intrauterine releasing system.
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Acknowledgments |
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Notes |
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References |
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Submitted on September 24, 1999; accepted on November 29, 1999.