Investigation of the infertile couple

Hysteroscopy with endometrial biopsy is the gold standard investigation for abnormal uterine bleeding

Ariel Revel,1 and Asher Shushan

Department of Obstetrics and Gynecology, The Hebrew University, Hadassah Medical Center, Kiryat Hadassah, POB 12000, IL-91120, Jerusalem, Israel


    Abstract
 Top
 Abstract
 Introduction
 Conclusions
 References
 
During the last decade hysteroscopy has become the tool of choice for the evaluation of the endometrial cavity, including for assessment of abnormal uterine bleeding (AUB). Many clinicians would consider that, in most patients, the combination of transvaginal sonography and out-patient endometrial biopsy with diagnostic hysteroscopy could replace the need for dilation and curettage. Hysteroscopy was reported to have sensitivity, specificity, negative predictive value and positive predictive value of 94.2, 88.8, 96.3 and 83.1% respectively, in predicting normal or abnormal endometrial histopathology. The highest accuracy of hysteroscopy was in diagnosing endometrial polyps, whereas the worst result was in estimating hyperplasia. Therefore, since the incidence of focal lesions in patients with AUB is high, it seems that the most beneficial approach is to proceed with hysteroscopy complemented by endometrial biopsy early in the assessment of AUB. Nevertheless, the usage of distension media to flush the uterine cavity raises the concern that when the endometrium harbours pathology, there is the potential risk of retrograde dissemination of malignant cells into the peritoneal cavity. The clinical significance of the dissemination of endometrial cells during hysteroscopy is still undetermined.

Key words: abnormal uterine bleeding/endometrial biopsy/hysteroscopy


    Introduction
 Top
 Abstract
 Introduction
 Conclusions
 References
 
Abnormal uterine bleeding (AUB) is the single most common reason for gynaecological referrals (Gimpelson and Rappold, 1988Go). While there are various benign reasons for AUB, abnormal peri- or post-menopausal bleeding is associated with endometrial cancer in ~10% of cases (Creasman, 1997Go). Just as Balasch has questioned the relative usefulness of conventional methods of infertility evaluation (Balasch, 2000Go), we here consider the methods used to investigate AUB. Most frequently, one of three invasive methods is used to assess AUB: dilatation and curettage (D&C), endometrial biopsy or hysteroscopy with or without directed biopsies.

The D&C procedure has traditionally been considered as standard for the investigation of AUB. However, several disadvantages of D&C have led investigators to look for alternatives to this procedure. The two main disadvantages are that in most cases D&C is performed under general anaesthesia, and that it is a blind procedure. In one study, 60% of patients had less than half the uterine cavity curetted and 16% had less than a quarter (Leather et al., 1991Go).

Histological evaluation could alternatively be obtained by office endometrial biopsy (i.e. using a ‘Pipelle’ catheter). This out-patient procedure is performed without uterine cervix dilatation, and therefore causes minimal discomfort. The sensitivity of endometrial biopsy for detecting endometrial cancer ranges from 67 to 96% (Brand, 2000Go). A critical review of 33 reports summarizing 13598 D&Cs and 5851 office biopsies showed that D&C had a higher complication rate than office biopsy, but that their diagnostic adequacy was comparable (Chambers and Chambers, 1992Go). The main disadvantage of the ‘blind’ endometrial biopsy is that it can miss a focal lesion like a polyp or a localized pathological lesion.

The ever increasing value of diagnostic and operative hysteroscopy for patients with AUB serves as an appropriate tribute to Pantaleoni, who in 1869 described this procedure to look inside the uterus (Pantaleoni, 1869). Contemporary instrumentation permits the gynaecologist to quickly acquire the basic skills necessary for routine performance of office-based hysteroscopy. Moreover, due to its higher diagnostic accuracy and suitability for out-patient investigation, hysteroscopy is increasingly replacing D&C for the evaluation of AUB (Wieser et al., 2001Go). Hysteroscopy is also becoming an integral part of the infertility work-up (Shushan and Rojansky, 1999Go).

Our experience with diagnostic hysteroscopies to investigate AUB has shown that this procedure is easy to perform, well tolerated by patients and can detect endometrial lesions even following negative endometrial sampling or D&C. Following normal endometrial histology of ‘blindly’ sampled uterine contents, hysteroscopy enabled a directed biopsy of suspicious intrauterine lesions which turned out in some cases to harbour endometrial cancer (Shushan et al., 2001Go, 2002Go). Moreover, hysteroscopic surgery is safe and effective for post-menopausal women with benign intrauterine lesions (Shushan et al., 2001Go). A study which compared hysteroscopy-based directed biopsies and D&C found that the results of hysteroscopy and curettage were in agreement in 223/276 cases (80.8%). Hysteroscopy revealed more information than curettage in 44 patients (16%), whereas curettage revealed more information than hysteroscopy in only nine patients (3.3%) (Gimpelson and Rappold, 1988Go). In a recent prospective study it was shown that curettage alone is not sufficient for detection and extraction of endometrial polyps. Curettage alone detected endometrial polyps in only 22 of 51 patients (43%) with polyps diagnosed by hysteroscopy (Gebauer et al., 2001Go). When the results of this study are combined with those of previous studies, there is little doubt that hysteroscopy is superior to D&C in making an accurate diagnosis of pathological conditions in the uterine cavity. Indeed, the combination of transvaginal sonography and out-patient hysteroscopy with endometrial biopsy has a similar efficacy to in-patient hysteroscopy and curettage for the investigation of AUB (Tahir et al., 1999Go).

The purpose of the invasive evaluation in patients with AUB is to detect pathology in the uterine cavity and specifically to detect endometrial cancer. Hysteroscopy was reported to have sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 94.2, 88.8, 96.3 and 83.1% respectively in predicting normal or abnormal endometrial histopathology (Garuti et al., 2001Go). The highest accuracy of hysteroscopy was in diagnosing endometrial polyps, whereas the worst result was in estimating hyperplasia. Indeed, in a recent study the sensitivity and PPV of hysteroscopy without endometrial biopsy in diagnosing endometrial carcinoma was only 58.8 and 20.8% respectively (Lo and Yuen, 2000Go). Therefore, since the incidence of focal lesions in patients with AUB is 46–74% (Nagele et al., 1996aGo,bGo; Pal et al., 1997Go), it seems that the most cost-effective approach is to proceed with hysteroscopy complemented by endometrial biopsy, early in the assessment of AUB.

Another diagnostic modality that might be used to evaluate patients with AUB is sonohysterography (SHG). SHG was shown to be significantly better than transvaginal ultrasonography in detecting focal intrauterine pathology in patients presenting with AUB. The use of saline infusion to enhance visualization of the endometrium increases the diagnostic accuracy of transvaginal sonography to approach that of diagnostic hysteroscopy, and also provides additional information on other pelvic structures. This development has implications for the management of uterine bleeding disorders. The overall sensitivity of transvaginal ultrasonography improved after SHG from 67 to 87% and the specificity from 89 to 91%. The PPV increased from 88 to 92% and the NPV from 71 to 86% (Schwarzler et al., 1998Go). The use of SHG also improved the quality of information about the location and size of polyps and submucous fibroids. Due to its convenience and diagnostic accuracy, some authors have recently shown that visual examination by hysteroscopy yielded no additional information to SHG (Krampl et al., 2001Go). However, several other groups have shown that hysteroscopy was more accurate in detecting intracavitary uterine pathology than transvaginal sonography (Paschopoulos et al., 2001Go).

A troubling issue is the possibility that reflux of endometrial cells during fluid-based hysteroscopy might cause retrograde dissemination of malignant cells into the peritoneal cavity. Retrospective data support a correlation between fluid-based hysteroscopy and the presence of cancer cells in the peritoneal cavity. However, it cannot be determined whether peritoneal washings ‘turned positive’ as a result of hysteroscopy or whether they were there in advance. The rate of positive peritoneal cytology in retrospective studies was 6.8 and 17.0% (Obermair et al., 2000Go; Zerbe et al., 2000Go). Surprisingly, this rate is similar to the 14.7% incidence of positive peritoneal cytology which was reported in a summary of 1541 patients suffering from endometrial cancer without previous hysteroscopy (Hacker, 1994Go). Since no prospective randomized study in clinical stage I endometrial carcinoma was performed on the dissemination of cancer cells by diagnostic hysteroscopy, no definite conclusions can be drawn and the clinical implications of such reflux have yet to be determined.


    Conclusions
 Top
 Abstract
 Introduction
 Conclusions
 References
 
AUB is a common gynaecological symptom. While most patients have benign disease, thorough investigation is necessary, particularly in peri- and post-menopausal woman. Hysteroscopy with endometrial biopsy should replace D&C as the method of choice for the investigation of AUB. In the majority of women this can be performed as an out-patient procedure with no loss in diagnostic accuracy. Hysteroscopy may help to identify pathological findings missed by endometrial biopsy and thus reassure the physician and his patient that a negative biopsy is the result of an atrophic mucosa. Endometrial sampling should be complementary to hysteroscopy as the latter is not sensitive enough in predicting normal or abnormal endometrial histopathology. The usage of distension media to flush the uterine cavity raises the concern that when the endometrium harbours pathology, there is the potential risk of retrograde dissemination of malignant cells into the peritoneal cavity, yet the clinical significance of the dissemination of such cells during hysteroscopy is still undetermined.


    Notes
 
1 To whom correspondence should be addressed. E-mail: arielrevel{at}hotmail.com Back


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 Introduction
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