Advertisement

Ultrasonography-based triage for perimenopausal patients with abnormal uterine bleeding

      Abstract

      OBJECTIVE: Abnormal perimenopausal bleeding is common and accounts for much medical and surgical intervention. This study was undertaken to evaluate an ultrasonography-based triage paradigm for perimenopausal patients with abnormal uterine bleeding. STUDY DESIGN: Four hundred thirty-three perimenopausal patients with abnormal uterine bleeding (either metrorrhagia, menorrhagia, or both) were evaluated. In lieu of undergoing a sampling procedure they were brought back on days 4 to 6 of the subsequent bleeding cycle, when the endometrium was expected to be its thinnest. If a distinct endometrial echo ≤5 mm (double layer) was imaged by endovaginal ultrasonography, dysfunctional uterine bleeding was diagnosed. If a thickened endometrial echo >5 mm or no endometrial echo was reliably visualized, a saline infusion sonohysterography was performed. If saline infusion sonohysterography revealed a symmetric single-layer endometrial thickness <3 mm, dysfunctional uterine bleeding was diagnosed. If focal lesions were noted (polyps, submucous myomas, focal thickening), the patient was scheduled for curettage with hysteroscopy. If the endometrium was globally thickened, nondirected office biopsy was performed. RESULTS: A total of 341 patients (79%) had ultrasonographic evidence of no anatomic abnormality, and dysfunctional uterine bleeding requiring no further studies was diagnosed. Fifty-eight patients (13%) had focal polypold masses, all of which were removed hysteroscopically and confirmed pathologically. Twenty-two patients (5%) had submucous myomas; 10 patients (23%) had globally thickened endometrium on saline infusion sonohysterography, and then nondirected office sampling revealed hyperplasia in 5 and proliferation in 5. Two patients had technically inadequate saline infusion sonohysterography, and thus we proceeded to hysteroscopy with curettage. CONCLUSION: Nondirected office biopsy alone without imaging would have potentially missed the diagnosis of focal lesions such as polyps, submucous myomas, and focal hyperplasia in up to 80 patients (18%). Our clinical algorithm for perimenopausal patients with abnormal uterine bleeding used unenhanced endovaginal ultrasonography followed by saline infusion sonohysterography for selected patients. This approach allowed for no endometrial sampling, nondirected sampling, or directed sampling depending on whether the ultrasonography-based triage revealed no anatomic abnormalities, globally thickened endometrial tissue, or focal abnormalities, respectively. (Am J Obstet Gynecol 1997;177:102-8)

      Keywords

      Up to 20% of office visits to the gynecologist are for abnormal vaginal bleeding.
      • Nesse R.
      Abnormal vaginal bleeding in perimenopausal women.
      Initially, curettage was the gold standard for evaluation of such patients.
      • Word B
      • Gravlee LC
      • Widemon GL.
      The fallacy of simple uterine curettage.
      Decades ago, however, misgivings about the accuracy and reliability as well as cost and risks of curettage were expressed.
      • Word B
      • Gravlee LC
      • Widemon GL.
      The fallacy of simple uterine curettage.
      • Stoch RJ
      • Kanbour A.
      Prehysterectomy curettage.
      Office endometrial sampling devices offered reduced expense, less anesthesia requirements, increased convenience, and increased safety.
      • Chambers J
      • Chambers S.
      Endometrial sampling: when? where? why? with what?.
      Such devices have been shown to have severe shortcomings, especially in cases in which the abnormality is focal and not global.
      • Guido RS
      • Kanbour A
      • Ruhn M
      • Christopherson WA.
      Pipelle endometrial sampling sensitivity in the detection of endometrial cancer.
      • Dubinsky TJ
      • Parvey HR
      • Gomez G
      • Curtis M
      • Maklad N.
      Transvaginal hysterosonography: Comparison with biopsy in the evolution of postmenopausal bleeding.
      Hysteroscopy with directed biopsy has been shown to be superior to curettage,
      • Gimpelson R
      • Roppold H.
      A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage.
      although this procedure requires specialized equipment and is very operator dependent.
      Endovaginal ultrasonography has been explored as an inexpensive, noninvasive, convenient way to indirectly visualize the endometrial cavity. It has been used most extensively in postmenopausal patients with abnormal bleeding. It has been shown to effectively exclude a lack of significant abnormality when the endometrial echo is ≤4 to 5 mm.
      • Nasri MN
      • Coast GJ.
      Correlation of ultrasound findings and endometrial histopathology in postmenopausal women.
      • Osmers R
      • Volksen M
      • Schnauer A.
      Vaginosonography for early detection of endometrial carcinoma?.
      • Goldstein SR
      • Nachtigall M
      • Snyder JR
      • Nactigall L.
      Endometrial assessment by vaginal ultrasonography before endometrial sampling in patients with postmenopausal bleeding.
      • Granberg S
      • Wikland M
      • Karlsson B
      • Norström A
      • Friberg L-G.
      Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality.
      Some investigators have looked at premenopausal women with endovaginal ultrasonography to exclude endometrial abnormalities in perimenopausal women with abnormal bleeding.
      • Smith P
      • Bakos O
      • Heimer G
      • Ulmsten U.
      Transvaginal ultrasound for identifying endometrial abnormality.
      • Dijkhuzien FPHLJ
      • Brolmann HAM
      • Potters AE
      • Bongers MY
      • Heinz AP.
      The accuracy of transvaginal ultrasonography in the diagnosis of endometrial abnormalities.
      We have previously shown that addition of saline infusion sonohysterography can reliably distinguish perimenopausal patients with dysfunctional abnormal bleeding (no anatomic abnormality) from those with globally thickened endometria or those with focal abnormalities.
      • Goldstein SR.
      Use of ultrasonohysterography for triage of perimenopausal patients with unexplained uterine bleeding.
      We undertook this study to evaluate a clinical algorithm in perimenopausal women with abnormal bleeding using unenhanced endovaginal ultrasonography, followed by saline infusion sonohysterography for selected patients, and then either no endometrial sampling, undirected endometrial sampling, or visually directed endometrial sampling, depending on whether the ultrasonography-based triage revealed no anatomic abnormality, globally thickened endometrium, or focal abnormalities, respectively.

      Material and methods

      Perimenopausal women with the chief complaint of abnormal vaginal bleeding were evaluated. Only women >39 years old but not yet clinically menopausal as defined by <6 months of amenorrhea were included. The patients all had either metrorrhagia, defined as vaginal bleeding separate from the expected menses, or menorrhagia, defined for this study as the patients' subjective complaints of either increased duration or increased volume of flow or both. Patients using oral contraceptives or hormone supplementation or having positive monoclonal antibody pregnancy test results were excluded. Instead of undergoing any invasive sampling, these patients were instructed to return on days 4 to 6 of the subsequent bleeding episode when the endometrium was expected to be as thin as it would be during the entire cycle. The ultrasonography-based clinical pathway as described in Fig. 1 was followed. Scans were performed with either a Siemens SI 400 5/6/7.5 MHz (Siemens Medical Systems, Issaquah, Wash.) endovaginal probe or an Aloka 650CL 5 MHz (Corometrics, Wallingford, Ct.) endovaginal probe. Endometrial thickness measurements were performed at the widest midline echo in the anterior-posterior plane on a long-axis view, and we were careful to scan the entire endometrial cavity as a three-dimensional structure from cornu to cornu and fundus to cervix to look for any focal abnormalities. Saline infusion sonohysterography was performed according to methods previously described.
      • Goldstein SR.
      Use of ultrasonohysterography for triage of perimenopausal patients with unexplained uterine bleeding.
      Undirected endometrial sampling, when indicated, was performed with a Pipelle (Unimar, Wilton, Ct.) aspiration device. Directed endometrial sampling was performed as part of a hysteroscopy with curettage while the patient was under general anesthesia in a day surgery setting.
      Figure thumbnail gr1
      Fig. 1Flow chart for perimenopausal patients with abnormal uterine bleeding. DX, Diagnosis; EM, endometrium; D&C, curettage.

      Results

      In 280 patients (65%) a thin, distinct, symmetric endometrial echo ≤5 mm was displayed on days 4 to 6, and dysfunctional uterine bleeding was diagnosed (Fig. 2).
      Figure thumbnail gr2
      Fig. 2Endovaginal ultrasonography on day 6 reveals a thin distinct endometrial echo measuring 2.1 mm (by calipers) on this long-axis view. This picture excludes significant abnormality and is most compatible with early proliferative tissue on histologic examination.
      One hundred fifty-three (35%) had saline infusion sonohysterography. Of these procedures, 44 (29%) were performed because of the inability to adequately characterize and measure the endometrium (Figs. 3 and 4) and 109 (71%) were done for endometrial measurement >5 mm (Table I). Sixty-one of these patients then had both anterior and posterior endometrial thickness that was symmetric and <3 mm, compatible with dysfunctional uterine bleeding. Fifty-eight patients (13%) had focal polypoid masses (Fig. 5) that were removed hysteroscopically and confirmed pathologically. Twenty-two patients (5%) had submucous myomas although 148 patients (34%) had clinical and ultrasonographic evidence of fibroids. Ten patients had single-layer measurements of endometrium on saline infusion sonohysterography >3 mm (range 3 to 9 mm). Histologic type was proliferative endometrium in 5 and hyperplastic endometrium in 5. Saline infusion sonohysterography was technically inadequate in 2 patients; we thus proceeded directly to hysteroscopy with curettage in these women (Table II). Undirected office biopsy alone without imaging potentially would have missed the diagnosis of focal lesions such as polyps, submucous myomas, and focal hyperplasia in up to 80 patients (18%).
      Figure thumbnail gr3
      Fig. 3Long-axis view of uterus in a patient with menometrorrhagia. Distinct endometrial echo is not well visualized. This is an indication for saline infusion sonohysterography.
      Figure thumbnail gr4
      Fig. 4Coronal view of patient depicted in Fig. 3. There is an anterior wall midline submucous myoma measuring 1.9 × 1.3 cm. The endometrium surrounding the fluid instillation is thin, indicative of early proliferative change.
      Table IUnenhanced vaginal ultrasonographic findings on days 4 to 6
      FindingNo.%
      Endometrial echo ≤5 mm28065
      Endometrial echo >5 mm10925
      Endometrial echo inadequately visualized4410
      total433100
      Figure thumbnail gr5
      Fig. 5Long-axis view of uterus in a patient with abnormal uterine bleeding. There is a polyp protruding from the anterior wall approximately halfway to the fundus. It measures 1.5 × 0.9 cm (by calipers). The echogenic endometrium that overlies the fluid lining the remainder of the cavity is thin and in the early proliferative stage, compatible with a lack of significant abnormality.
      Table IISaline infusion sonohysterograms
      FindingNo.%
      Thin endometrium (anterior and posterior wall ≤3 mm6140%
      Polypoid masses5838%
      Submucous myomas2214%
      Thick symmetric endometrium (anterior and posterior wall >3 mm)107%
      Inadequate saline infusion sonohysterogram21
      total153100

      Comment

      Clearly, a perimenopausal patient with abnormal uterine bleeding needs evaluation. The vast majority will have dysfunctional uterine bleeding in association with episodes of anovulation that can best be managed hormonally or expectantly with reassurance. The value of an approach to distinguish such patients from those with organic pathologic conditions in a safe, painless, convenient manner is obvious.
      Previously, curettage was the gold standard. First described
      • Ricci JV.
      Gynaecologic surgery and instruments of the nineteenth century prior to the antiseptic age.
      by Recomier in 1843, its performance in the hospital became the most common operation performed on women in the world. As early as the 1950s, a review of 6907 curettage procedures by Word et al.
      • Word B
      • Gravlee LC
      • Widemon GL.
      The fallacy of simple uterine curettage.
      found the incidence of perforation in premenopausal women to be 1 in 325. The technique missed endometrial lesions in 10% of cases. Of these, 80% were polyps. Stoch and Kanbour
      • Stoch RJ
      • Kanbour A.
      Prehysterectomy curettage.
      in a study of curettage before hysterectomy found that “in 16% of specimens less than one quarter of the cavity was curetted, in 60% less than one half of the cavity was curetted, and in 84% less than three quarters of the endometrial cavity had been effectively curetted.”
      In the 1970s, vacuum-suction curettage devices allowed sampling without anesthesia in an office setting. The most popular was the Vabra (Berkeley Medevices, Berkeley, Calif.) aspirator. This was found to be 86% accurate in diagnosing cancer.
      • Vuopala S.
      Diagnostic accuracy and clinical applicability of cytological and histological methods for investigating endometrial carcinoma.
      Subsequently, cheaper, smaller, less painful plastic catheters with their own internal pistons to generate suction became popular. One of these, the Pipelle device, was found to have similar efficacy but better patient acceptance when compared with the Vabra.
      • Kaunitz AM
      • Masciello AS
      • Ostrowsky M
      • Rovvira EZ.
      Comparison of endometrial Pipelle and Vabra aspirator.
      • Eddowes HA.
      Pipelle: a more acceptable technique for outpatient endometrial biopsy.
      In one widely publicized study by Stovall et al.
      • Stovall TG
      • Photopulos GJ
      • Poston WM
      • Ling FW
      • Sandles LG.
      Pipelle endometrial sampling in patients with known endometrial cancer.
      the Pipelle had a 97.5% sensitivity to detect endometrial cancer in 40 patients undergoing hysterectomy. The shortcoming of this study was that the diagnosis of malignancy was known before the performance of the specimen collection.
      Goldchmit et al.
      • Goldchmit R
      • Katz Z
      • Blickstein I
      • Caspi B
      • Dgani R.
      The accuracy of endometrial Pipelle sampling with and without sonographic measurement of endometrial thickness.
      performed Pipelle aspiration biopsy in 135 premenopausal patients before curettage. Thirteen patients (10%) had different histologic results on Pipelle biopsy as compared with curettage. It is interesting that only 5 of their patients had polyps, of which Pipelle sampling missed 3. In total, 18 patients had hyperplasia, of which Pipelle sampling missed the diagnosis in 7 (39%), thus underscoring the often focal nature of that pathologic process. The actual Pipelle biopsy findings in those 7 patients with false-negative results that ultimately were cases of hyperplasia were proliferative endometrium in 2, endocervical tissue in 1, tissue insufficient for diagnosis in 3, and endometritis in 1.
      Rodriguez et al.
      • Rodriguez MH
      • Platt LD
      • Medearis AL
      • Lacarra M
      • Lobo RA.
      The use of transvaginal sonography for evaluation of postmenopausal size and morphology.
      did a pathologic study of 25 hysterectomy specimens. The percentage of endometrial surface sampled by the Pipelle device was 4% versus 41% for the Vabra aspirator. Guido et al.
      • Guido RS
      • Kanbour A
      • Ruhn M
      • Christopherson WA.
      Pipelle endometrial sampling sensitivity in the detection of endometrial cancer.
      also studied the Pipelle biopsy in patients with known carcinoma undergoing hysterectomy. Among 65 patients Pipelle biopsy provided tissue adequate for analysis in 63 (97%). Malignancy was detected in only 54 patients (83%). Of the 11 with false-negative results, 5 (8%) had disease confined to endometrial polyps and 3 (5%) had tumor localized to <5% of the surface area. The surface area of the endometrial involvement in that study was ≤5% in 3 of 65 (5%); 5% to 25% in 12 of 65 (18%), of which the Pipelle missed 4; 26% to 50% in 20 of 65 (31%), of which the Pipelle missed 4; and >50% in 30 of 65 patients (46%), of which the Pipelle missed none. These results tell us a great deal about the way endometrial carcinoma can be distributed over the endometrial surface or confined to a polyp. Because tumors localized in a polyp or a small area of endometrium may go undetected, Guido et al. concluded that the “Pipelle is excellent for detecting global processes in the endometrium.”
      Thus from these data we conclude that undirected sampling, whether through curettage or various types of suction aspiration, will often be fraught with error, especially in cases in which the abnormality is not global but focal (polyps, focal hyperplasia, or carcinoma involving small areas of the uterine cavity).
      Hysteroscopy provides direct visualization of the endometrial cavity. However, it is very operator dependent. It often requires ambulatory surgery centers and general anesthesia, or when it is performed as an office procedure with local or no anesthesia, it can potentially result in significant patient discomfort. It requires specialized equipment. Gimpelson and Roppold
      • Gimpelson R
      • Roppold H.
      A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage.
      compared results of 276 panoramic hysteroscopically directed biopsies with those of curettage. Overall agreement in the histologic findings was 81%. In 16% directed biopsy resulted in more histologic information than curettage gave. In 3% curettage was more revealing. Curettage primarily missed polyps and submucous myomas. The incidence of cancer was 0.9%. Both methods detected all three cancer cases.
      Studies like these suggest that the reliability of hysteroscopy is high although it remains very operator dependent. Chambers and Chambers
      • Chambers J
      • Chambers S.
      Endometrial sampling: when? where? why? with what?.
      concluded that “the expense and time involved in the use of the hysteroscope are not justified for routine evaluation of all women with abnormal uterine bleeding.” Clearly, a prospective, randomized clinical trial comparing hysteroscopically directed sampling with curettage in which the subsequent hysterectomy specimen itself serves as the gold standard would be helpful.
      Ultrasonography is a safe, readily available modality for noninvasively imaging the endometrial cavity. In our opinion it can allow “visualization” similar to hysteroscopy, especially if one resorts to saline infusion sonohysterography. Unenhanced endovaginal ultrasonography has been used to reliably predict lack of significant abnormality in postmenopausal women with bleeding.
      • Nasri MN
      • Coast GJ.
      Correlation of ultrasound findings and endometrial histopathology in postmenopausal women.
      • Osmers R
      • Volksen M
      • Schnauer A.
      Vaginosonography for early detection of endometrial carcinoma?.
      • Goldstein SR
      • Nachtigall M
      • Snyder JR
      • Nactigall L.
      Endometrial assessment by vaginal ultrasonography before endometrial sampling in patients with postmenopausal bleeding.
      • Granberg S
      • Wikland M
      • Karlsson B
      • Norström A
      • Friberg L-G.
      Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality.
      Measurements ≤4 to 5 mm have consistently been shown to be highly associated with lack of significant tissue. It should be stressed that a reliable assessment with ultrasonography requires that the endometrial echo be homogeneous, surrounded by an intact hypoechoic junctional zone, and that the operator constantly remember that the endometrial cavity is a three-dimensional structure. This may account for why Dijkhuzien et al.
      • Dijkhuzien FPHLJ
      • Brolmann HAM
      • Potters AE
      • Bongers MY
      • Heinz AP.
      The accuracy of transvaginal ultrasonography in the diagnosis of endometrial abnormalities.
      had four cases that supposedly measured <10 mm (some as little as 2 mm) and yet at hysteroscopy displayed polyps. They did not describe or show pictures of these cases, but one is left to conclude that these cases underscore the importance of the three-dimensional character of the endometrial cavity and the occasional propensity of the ultrasonographic operator to obtain a limited number of two-dimensional views and assume that these represent the entire endometrial cavity. Any one “frozen” ultrasonographic image is nothing more than a two-dimensional “snapshot,” and failure to meticulously recreate three-dimensional anatomy will result in error.
      In the study of Dijkhuzien et al.
      • Dijkhuzien FPHLJ
      • Brolmann HAM
      • Potters AE
      • Bongers MY
      • Heinz AP.
      The accuracy of transvaginal ultrasonography in the diagnosis of endometrial abnormalities.
      18 of 69 women (26%) were noted to have hysteroscopically detected focal endometrial abnormality that curettage alone failed to detect. This compares with our prevalence of focal abnormality of 18% (80/433). Dijkhuzien et al. further used a single-layer measurement of 5 mm as a cutoff for premenopausal women. This is equivalent to 10 mm in our full-thickness measurements. They concluded that even at that level such endometrial measurements “represent a very small risk for endometrial abnormality. If ultrasonography would have been used as a first step to decide on further examination invasive endometrial investigations would have been avoided in 40% (27/67) premenopausal women.”
      In our study 65% of patients required an unenhanced ultrasonography study alone, whereas 35% required saline infusion sonohysterography with or without undirected or directed endometrial sampling. We acknowledge that one limitation of our study is the inability to absolutely prove that unenhanced endovaginal measurements ≤5 mm or saline infusion sonohysterography single-layer measurements ≤3 mm will be devoid of abnormality. Unfortunately, however, short of comparison with hysterectomy specimens no true “gold standard” really exists. We have relied heavily on previous data, first in the form of our pilot study
      • Stovall TG
      • Photopulos GJ
      • Poston WM
      • Ling FW
      • Sandles LG.
      Pipelle endometrial sampling in patients with known endometrial cancer.
      wherein the thickest single-layer measurement on days 4 to 6 of a bleeding cycle associated with proliferative endometrium was 3.2 mm. Furthermore, we have relied on numerous published studies
      • Nasri MN
      • Coast GJ.
      Correlation of ultrasound findings and endometrial histopathology in postmenopausal women.
      • Granberg S
      • Wikland M
      • Karlsson B
      • Norström A
      • Friberg L-G.
      Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality.
      in which unenhanced vaginal ultrasonography ≤5 mm was associated with lack of significant pathologic tissue. Indeed, this was the basis for construction of our algorithm. The true value of our algorithm comes not from an ability to predict abnormality but from identifying patients who by ultrasonography can avoid further interventions, as well as distinguishing those patients whose abnormalities are focal and need directed sampling versus those who can undergo global sampling and have undirected aspiration tissue sampling. Thus, in summary, we believe, on the basis of both our data and prior studies cited, that undirected endometrial sampling is unnecessary if unenhanced endovaginal ultrasonography clearly shows a distinct homogeneous endometrium ≤5 mm early in the proliferative phase, when the endometrium will be at the thinnest it should be all month long. We further hold that single-layer anterior and posterior endometrial measurements ≤3 mm at the time of saline infusion sonohysterography exclude significant abnormality. We contend that undirected endometrial sampling is only appropriate if one first demonstrates that the endometrial process is indeed global and not focal. Finally, we believe that hysteroscopy with curettage should be reserved for those patients with demonstrated focal abnormality on saline infuision sonohysterography who are in need of visually directed removal or whose ultrasonographic triage was technically unable to exclude significant abnormality.

      References

        • Nesse R.
        Abnormal vaginal bleeding in perimenopausal women.
        Am Fam Phys. 1989; 40: 185-189
        • Word B
        • Gravlee LC
        • Widemon GL.
        The fallacy of simple uterine curettage.
        Obstet Gynecol. 1958; 12: 642-645
        • Stoch RJ
        • Kanbour A.
        Prehysterectomy curettage.
        Obstet Gynecol. 1975; 45: 537-541
        • Chambers J
        • Chambers S.
        Endometrial sampling: when? where? why? with what?.
        Clin Obstet Gynecol. 1992; 35: 28-39
        • Guido RS
        • Kanbour A
        • Ruhn M
        • Christopherson WA.
        Pipelle endometrial sampling sensitivity in the detection of endometrial cancer.
        J Reprod Med. 1995; 40: 553-555
        • Dubinsky TJ
        • Parvey HR
        • Gomez G
        • Curtis M
        • Maklad N.
        Transvaginal hysterosonography: Comparison with biopsy in the evolution of postmenopausal bleeding.
        J Ultrasound Med. 1995; 14: 887-893
        • Gimpelson R
        • Roppold H.
        A comparative study between panoramic hysteroscopy with directed biopsies and dilatation and curettage.
        Am J Obstet Gynecol. 1988; 158: 489-494
        • Nasri MN
        • Coast GJ.
        Correlation of ultrasound findings and endometrial histopathology in postmenopausal women.
        Br J Obstet Gynaecol. 1989; 96: 1333-1338
        • Osmers R
        • Volksen M
        • Schnauer A.
        Vaginosonography for early detection of endometrial carcinoma?.
        Lancet. 1990; 335: 1569-1571
        • Goldstein SR
        • Nachtigall M
        • Snyder JR
        • Nactigall L.
        Endometrial assessment by vaginal ultrasonography before endometrial sampling in patients with postmenopausal bleeding.
        Am J Obstet Gynecol. 1990; 163: 119-123
        • Granberg S
        • Wikland M
        • Karlsson B
        • Norström A
        • Friberg L-G.
        Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality.
        Am J Obstet Gynecol. 1991; 164: 47-52
        • Smith P
        • Bakos O
        • Heimer G
        • Ulmsten U.
        Transvaginal ultrasound for identifying endometrial abnormality.
        Acta Obstet Gynecol Scand. 1991; 70: 591-594
        • Dijkhuzien FPHLJ
        • Brolmann HAM
        • Potters AE
        • Bongers MY
        • Heinz AP.
        The accuracy of transvaginal ultrasonography in the diagnosis of endometrial abnormalities.
        Obstet Gynecol. 1996; 87: 345-349
        • Goldstein SR.
        Use of ultrasonohysterography for triage of perimenopausal patients with unexplained uterine bleeding.
        Am J Obstet Gynecol. 1994; 170: 565-570
        • Ricci JV.
        Gynaecologic surgery and instruments of the nineteenth century prior to the antiseptic age.
        in: The development of gynaecological surgery and instruments. Blakiston, Philadelphia1949: 326-328
        • Vuopala S.
        Diagnostic accuracy and clinical applicability of cytological and histological methods for investigating endometrial carcinoma.
        Acta Obstet Gynecol Scand Suppl. 1997; 70: 1
        • Kaunitz AM
        • Masciello AS
        • Ostrowsky M
        • Rovvira EZ.
        Comparison of endometrial Pipelle and Vabra aspirator.
        J Reprod Med. 1988; 33: 427-431
        • Eddowes HA.
        Pipelle: a more acceptable technique for outpatient endometrial biopsy.
        Br J Obstet Gynaecol. 1990; 97: 961-962
        • Stovall TG
        • Photopulos GJ
        • Poston WM
        • Ling FW
        • Sandles LG.
        Pipelle endometrial sampling in patients with known endometrial cancer.
        Obstet Gynecol. 1991; 77: 954-956
        • Goldchmit R
        • Katz Z
        • Blickstein I
        • Caspi B
        • Dgani R.
        The accuracy of endometrial Pipelle sampling with and without sonographic measurement of endometrial thickness.
        Obstet Gynecol. 1993; 82: 727-730
        • Rodriguez MH
        • Platt LD
        • Medearis AL
        • Lacarra M
        • Lobo RA.
        The use of transvaginal sonography for evaluation of postmenopausal size and morphology.
        Am J Obstet Gynecol. 1988; 159: 810-814