Introduction

Traditionally, abnormal uterine bleeding (AUB) is defined as bleeding which is abnormal in volume, regularity, and /or timing^[1] is common and affects 14-25% of women of reproductive age.^[2], ^[3], ^[4] AUB has a major impact on quality of life^[5] and leads to 3.5 million days of work absence,^[6] and generates significant health care costs. FIGO has recommended PALM-COEIN Classification where PALM (Polyp, Adenomyosis, Leomyoma, Malignancy) denotes the structural causes while COEIN (Coagulopathy, Ovulatory dysfunction, endometrial, iatragenic and not yet classified) stands for functional causes of AUB. For maintaining the uniformity in terminologies it is recommended to describe irregularity of the cycle such as, Heavy flow with normal duration (HMB), Heavy flow with prolonged duration, Inter menstrual bleeding (IMB).^[1], ^[7], ^[8]

Aetiology of AUB may be structural and functional and varies with the age group. Histological pattern of endometrial sampling along with clinical and radiological findings remains the diagnostic standard for clinical diagnosis of endometrial pathology which ultimately helps in deciding the management of patients.^[9]

Although transvaginal sonography (TVS) is primarily used for evaluation of AUB however histopathological diagnosis is possible with endometrial sampling by pipelle, dilatation and curettage (D & C) and hysteroscopy guided endometrial biopsy plays an important role in formulating treatment of AUB.

Materials and Methods

A single center prospective cross-sectional study at PCMC’S PGI and Y C M Hospital, Pune was carried out from 1^st Jan 2020 to 31^st May 2021. Total 150 female were ([Figure 1]) enrolled between age group 18 to 70 who presented with Abnormal Uterine bleeding. Endometrial biopsy sample was obtained either by OPD Pipelle brush or by Surgical Dilatation and Curettage method or hysteroscopy along with endometrial biopsy. Histopathological diagnoses were studied for all samples. Data was collected in the standard format mentioned in the data collection tool ([Table 1]). Statistical Analysis was done by using Epi-Info-7 software. Informed consent obtained from all participants.

Objectives

Results

[Table 2] shows most of our patients are para 3 or more 96 cases (64%) cases and most patients 82 cases (54.6%) belong to lower socio economic class.

[Table 2], [Table 3] shows age group wise spectrum of endometrial pathologies in patients with AUB. In age group 21-30 years 7 cases (4.5%) underwent endometrial sampling and histological features in this age group were mainly benign changes such as proliferative and pill endometrium 2 cases each, secretary change, chronic endometritis, polyp one case each. Age group 31-40 years 53 cases (35.3%) underwent endometrial sampling and histological changes were mostly benign such as proliferative (23), secretary (11) pill endometrium (2) endometrial hyperplasia without atypia (4) with atypia (2) chronic endometritis and endometrial polyp 3 cases each and inadequate sample in 2 cases. Age group 41-50 contributed to maximum number 60 cases (40%) and endometrial changes were Proliferative (22), secretary (12), endometrial hyperplasia without atypia (7), with atypia (3) carcinoma endometrium (1), other changes were chronic endometritis (6), pill endometrium (1), Polyp. (2) Age group 51-60 contributed 22 cases 14% of cases and histopathological changes were noted as proliferative (6), disordered proliferative (1), Atrophic endometrium and chronic endometritis 2 cases each, endometrial hyperplasia without atypia (6), with atypia (2), carcinoma endometrium (1), inadequate sample (1) other changes were benign. Age group 61-70 total 8 cases (5.2%) underwent endometrial sampling and pathological changes were endometrial carcinoma (3), atrophic endometrium (3) and endometrial polyp (1), inadequate sample for reporting (1). Repeat endometrial sampling was done in cases after inadequate sample it is reported as chronic endometritis in one case and atrophic endometrium in 2 cases in this age group.

[Table 4] shows commonest clinical presentation as heavy menstrual bleeding HMB with normal duration 96 cases (64%), followed by heavy and prolonged bleeding in 23 cases (15.3%), Post menopausal bleeding 23 cases (15.3%), Intermenstrual bleeding (IMB) was presentation in 8 cases 5.4%.

[Table 5] shows out of 150 patients out 71 patients subjected to pipelle biopsy only 69 cases sample was obtained while 2 cases technical failure was noted in pipelle group. 34 patients endometrial sample was obtained by traditional dilatation and curettage technique while 47 cases underwent hysteroscopy along with endometrial biopsy and additional 3 cases who consented for repeat sampling by hysteroscopy due to inadequate sample for reporting also underwent (total 50 cases) hysteroscopy. Inadequate sample was noted in 4 (5.6%) cases in pipelle group and in 3 (8.8%) cases in D & C group. One Uterine perforation (2.9%) was noted in patients undergoing dilatation and curettage. Pipelle biopsy was found to be more feasible for outpatient procedure however dilatation and curettage and hysteroscopy with biopsy were less feasible in our setting.

Discussion

AUB may be due to structural or functional causes and histopathological pattern of endometrial sampling along with clinical history and imaging (TVS) remains cornerstone of management of AUB.^[9]

Menstrual disorders are more common with advancing age. In our study ([Table 2]), below 30 years 7 cases (4.5%) underwent endometrial sampling. Incidence of AUB may be more in this age group however most cases being low risk are managed conservatively and are not subjected to endometrial sampling. Patients with high risk factors such as obesity or family history of endometrial cancer or non-response to medical management are generally subjected to endometrial sampling. Most common age group presenting with AUB in our study was 41-50 years 60 cases (40%) followed by 53 cases (35.3%) in 31-40 age group and this 31-50yr age group combined contributed to 75.3% cases. Similar finding have been reported by Doraiswami S et al.^[10] A similar incidence was reported by Yusuf et al^[11] and Muzaffar et al.^[12] in their study. After the age of 50 that is 51-60 year age group and 61-70 year age group had 22 cases (15%) and 8 cases (5.3%) respectively and this age group (51-70 years) together constituted 30 cases (20%) of our patients. However, this age group showed significant changes such as endometrial carcinoma and precursors for endometrial cancer such as endometrial hyperplasia without atypia and with atypia as discussed below.

96 cases ([Table 2]) out of 150 patients with AUB were para 3 or more and nulliparous were only 2.7% in our study. Nulliparous patients less commonly presents with AUB as compared to multiparous patients similar finding is observed in other studies.^[13], ^[14], ^[15] Patients attending health facilities in public sector are mainly from lower socio economic class contributed to 82 cases (54.6%) in our study.

[Table 3] shows functional endometrium with proliferative and secretary changes were noted in 53 cases (35.4%) and 24 cases (16%) respectively while Kafle et al^[9] in a study of 166 samples noted proliferative and secretary changes in 42.97% and 14.46% cases. Brahmaiah J et al.^[16] in study of 210 samples noted proliferativeand secretary changes in 31.3% and 11.43% cases respectively. Endometrial hyperplasia without atypia was seen in 18 cases (12%) cases and with atypia was seen in 7 cases (4.66%) in our study while Kafle et al^[9] noted hyperplasia of endometrium without atypia in 7.23% cases and atypical hyperplasia in 3.01% cases. Brahmaiah J et al^[16] noted endometrial hyperplasia in 20% cases with no specification of features such as atypia or without atypia. Various other authors have noted endometrial hyperplasia 6% to 26% of samples.^[16] Endometrial hyperplasia with or without hyperplasia should be given immediate attention and patients should be counselled regarding the nature of pathology detected and appropriate treatment to be instituted. Incidence of co-existing endometrial carcinoma ranges 6.4-43% in women undergoing hysterectomy for atypical hyperplasia.^[17] Natural history of endometrial hyperplasia without atypia suggest that risk of progression to endometrial is 2% if remains untreated and this figure is 23-29% for atypical hyperplasia.^[18]

In our study endometrial carcinoma is noted in 5 cases (3.3%) while Kafle N et al^[9] has reported 2.4% incidence of malignancy which were adenocarcinoma. Brahmaiah J et al.^[16] reported 0.47% incidence of malignancy in endometrial sample while various authors have mentioned 0.48 to 6.4% incidence of carcinoma endometrium in patients presenting with AUB.^[16] Incidence of finding carcinoma in endometrial sample varies with the population screened. AUB patients attending general gynaecology outpatient department, inclusive of all age group may have lower incidence of detection of carcinoma while screening of patients with high risk factors such as obesity, nulliparity, family history or samples from oncological hospital will report higher detection rate for malignancy.

Atrophic endometrium is noted in 6 cases (4%) in our study which is similar to rate 3.35% reported by Brahmaiah J et al^[16] and various authors reported rate of atrophic endometrium from 2-7.38%^[16] Rupture of dilated blood capillaries beneath the surface of atrophic endometrium may be responsible for the bleeding in these patients. Study by Doraiswami et al^[10] documented 2.4% incidence of atrophic endometrium while Dwivedi et al^[19] has reported 11% atrophic endometrium which is higher than our present reported incidence.

Endometrial polyp was reported in 8 cases (5.3%) cases in our study while Kafle N et al^[9] has reported 2.41% incidence of polyp. Brahmaiah J. et al^[16] has reported 0.95% incidence of endometrial polyp in AUB patients. Prevalence of endometrial polyp increase with age, endometrial polyp in postmenopausal women (11.8%) and premenopausal women in (5.8%) have been reported.^[20] Sometimes cervical polyp may be seen on speculum examination which may be symptomatic or asymptomatic. Symptomatic cervical polyp may be associated with endometrial polyps and hyperplasia more commonly in perimenopausal and post menopausal women. Endometrial abnormalities are noted in upto 55% of postmenopausal women with cervical polyp and these women should be offered endometrial sampling with hysteroscopy in addition to avulsion of polyp.^[21]

Heavy menstrual bleeding with normal duration was commonest presentation 96 cases (64%) in our study. Vijayraghavan et al^[22] has reported menorrhagia in 71.25% as the commonest presenting complaint in AUB patients while Kafle N et al^[9] has reported 58.43% of AUB cases with menorrhagia as presenting complaint. Postmenopausal bleeding (PMB) was presentation in 23 cases (15.3%) cases in our study while Kafle N et al^[9] has reported 19.27% incidence of PMB and Vijayraghavan et al^[22] has reported 12.5% incidence of PMB in patients with AUB. PMB should be evaluated properly to rule out sinister pathology as 90% of women with EC present with PMB, but over 90% of women with PMB have a benign underlying cause for their symptom.^[23], ^[24] Heavy and prolonged bleeding was noted in 23 cases (15.4%) cases in our study, while inter menstrual bleeding (IMB) was seen in 8 cases (5.4%). Kafle N et al^[9] and Vijayrghavan et al^[22] have reported 15.1% and 15% incidence of metrorrhagia in AUB patients respectively.

[Table 3], [Table 5] Technical failure was noted in 2 cases out of 69 cases (2.8%) of pipelle biopsy group. These 2 cases were also underwent repeat sampling by hysteroscopy. Overall technical failure was seen in 2 cases (1.33%) however technical failure was not seen in D & C and Hysteroscopy group in our study. Failed endometrial sampling is usually associated with pain or cervical stenosis, which is more common in nulliparous women.^[25] Pipelle endometrial biopsy is an opd procedure and quick to perform however failure of the procedure in 11% cases and inadequate sample 31%, pain, bleeding, infection and very rarely perforation have been reported,^[26] while failure rate for operative hysteroscopy 3.4% and ambulatory procedure 4.2% have been reported in the literature.^[26] In our study inadequate sample was obtained in 7 cases (4.6%) overall and 5.6% (N1= 69) in pipelle group and 8.8% (N2 =34) in D & C group. These patients were offered endometrial sampling by hysteroscopy for which 3 out of 7 patients consented and underwent repeat sampling by hysteroscopy. Previously it was thought that women with an inadequate sample can be reassured safely regarding non sinister pathology however study has shown 4.5% of women who were diagnosed with endometrial carcinoma had initial inadequate sample^[27] hence it is not appropriate to reassure the patient on the ground of inadequacy of the sample however preoperative high risks factors such as obesity, family history and supporting investigations such as endometrial thickness on TVS, irregularity of the endometrium are to be taken into account before reassuring, As a blind procedure endometrial sampling (pipelle or dilatation and curettage) has potential to miss small, localised cancers,^[28] women with benign or inconclusive histology, but persistent symptoms or suspicious ultrasound finding should be offered hysteroscopy.

Out of 71 cases ([Table 5]) which were subjected to endometrial sampling by pipelle among 2 cases there was technical failure in nulliparous and postmenopausal patients due pinpoint os or stenosed cervix and patients subsequently subjected to hysteroscopy with biopsy under anaesthetia for obtaining the sample. Hence, only 69 cases endometrial sample was obtained by pipelle biopsy out of 71 procedures. Technical failure was not observed with D & C (34 cases) as well as hysteroscopy procedure (47 cases) for obtaining the endometrial sample. The efficacy of Dilatation and Curettage as a sampling tool has been questioned^[29] however D & C still remains the choice for clinicians due to lack of availability of hysteroscope or cost factor for the patients.. Obtaining scant tissue and not covering the entire endometrium are the drawbacks of D & C. Hence histopathological report needs to be interpreted keeping patients history in mind to avoid under or overtreatment of patient. Pipelle biopsy was more feasible to use for outpatient services while Dilatation and curettage as well as Hysteroscopy with biopsy required of admission of patient, use of anaesthetia and prolonged stay and hence these methods were less feasible as compared to pipelle biopsy. Though outpatient hysteroscopy with biopsy is possible with miniature 2.9mm scope due non-availability of same patients were subjected to procedure under anaesthetia with 4.9 mm hysteroscope. In our study one case of uterine perforation (out of 34 cases 2.9%) while performing dilatation and curettage which was managed conservatively, however uterine perforation can occur with during hysteroscopy or pipelle biopsy. Average incidence of uterine perforation has been reported as 0.002-1.7% during hysteroscopy.^[30] In our study hysteroscopy group did not had perforation. Postmenopausal, pregnancy, peurperieum, acutely anteverted and retroverted uterus, or septic conditions are high risk factors for peforation. Perforations are more likely to happen when junior staff is performing the procedure. Experienced surgeon performing the procedure especially in presence of high risk factors will not only reduce the risk of perforation but can reduce the morbidity by early detection and prompt management.

In summary main findings of our study are, AUB is commonly in age group 41-50 followed by in the age group of 31-40. Higher parity (para 3 more) is associated with AUB. Functional endometrium with proliferative (35.4%) and secretary changes (16%) were commonly seen in AUB patients. Endometrial polyp was noted in 5.3% cases and precursor lesions for malignancy such as endometrial hyperplasia without atypia 12% and with atypia 4.7% and endometrial cancer was reported in 3.3% cases. In 7 (4.6%) cases endometrial sample obtained was inadequate for reporting and technical failure was noted in 2 (1.33%) cases out of 150 cases however technical failure was exclusively seen in pipelle group with technical failure rate of 2.8% of all pipelle proceudres, uterine perforation was noted in one case out of 150 cases (0.66%).

Strength and Limitations

Strength of study include prospective data collection in systematic manner for enrolled cases however study was limited to clinical and histopathological diagnoses while inclusion of treatment and comparison of histopathology after surgical management with the preoperative findings would have given more information about sensitivity and specificity about the endometrial sampling technique. Study is conducted in tertiary teaching hospital in gynaecology department and results of study may be generalised to all age group patients of similar population with complaints suggestive of AUB however incidences of pathology may vary if the age group of screened population differs (e.g. post menopausal) or patients have high risk factors such as patients attending oncological OPD.

Conclusion

Pipelle biopsy is feasible as quick and outpatient procedure however possibility of technical failure should be born in mind. Cases of inadequate sample should be analysed carefully with reference to background history, high risk factors, TVS imaging (endometrial thickness, irregularity of endometrium) and need for repeat sample and use of hysteroscopy to be considered case to case basis. This will help in case management as well as avoid over treatment or under treatment of underlying pathology.

Authors Contributions

MA, IR, MS, ST, SR involved in all processes of this research work. All authors read and approved the final manuscript. Conceived and designed the experiments: MA, MS.

Sources of Funding

None.

Conflict of Interest

None.

Ethical Approval

Yes Letter no. YCMH/PG/ETHICS/11/2019 dated 01/11/2019.