A descriptive study of Endometrial Biopsies in perimenopausal women having Abnormal uterine bleeding

Abnormal uterine bleeding (AUB) is one of the commonest symptom with which the perimenopausal female visits the gynaecologist accounting for over 70% of all gynecological consultations in that age group. The clinical presentation of AUB can range anywhere menorrhagia, polymenorrhea, polymenorrhagia, metrorrhagia, and menometrorrhagia. Though biopsy is the gold standard it is an invasive procedure and hence often an Ultrasound is used to evaluate the pathology of the endometrium routinely hence, we decided to study the accuracy between radiological ET thickened and its usefulness in detecting endometrial pathology. This study was carried out in the Department of Pathology at AJIMS, Mangalore for a period of 2 years. The sample included endometrial biopies and hysterectomy specimens of perimenopausal women for AUB. The ultrasonographic findings and Histopathological (HPE) reports were analysed. Among 101 cases for AUB, 67 cases were diagnosed as non secretory endometrium. Out of these 67 cases, 49 cases were associated with fibroids. Out of the rest of the AUB cases, 31 of them were diagnosed to have endometrial hyperplasia and 3 cases were diagnosed to have endometrial carcinoma. USG thickness of 17(54%) out of 31 endometrial hyperplasia cases were abnormal. Radiological and pathological evaluation were concordant with diagnosis of AUB associated with fibroids. However only 54% of the endometrial hyperplasia were found to have abnormal endometrial thickness. Radiological evaluation of endometrial thickness is not concordant in 46 % of the cases. This implies that histopathological examination is gold standard diagnostic tool for endometrial abnormalities in perimenopausal women.

Histopathological evaluation of endometrial sampling in perimenopausal women with abnormal uterine bleeding

Background: Abnormal uterine bleeding (AUB) is one of the common symptoms in the gynaecology outpatient department. About one third of women are affected at some time in their lives. The perimenopausal women show significant number of underlying organic pathology. The evaluation of endometrium and/or organ histopathology has the dual advantage of finding the cause of AUB and to rule out endometrial cancer or the potential for cancer in future like endometrial hyperplasia with atypia. The aim of the study was to determine the histopathological pattern of endometrial sampling in perimenopausal women with AUB and to follow them up for a period of six months after the procedure.Methods: The prospective observational study was conducted at the department of obstetrics and gynaecology at Sree Gokulam Medical College and Research Foundation, Venjaramood, Thiruvananthapuram, Kerala, for a period of one year from December 2019 to December 2020. The study was conducted on 116 perimenopausal women 41-52 years who presented with AUB and had undergone endometrial sampling. These ladies were subsequently followed up for six months post procedure to assess the response to medical treatment or the need for any surgical intervention like hysterectomy.Results: A total 39.65% patients had heavy and prolonged menstrual bleeding and 18.16% patients had irregular bleeding. 14.65% patients had prolonged flow, 8.6% had heavy flow, 6.8% had infrequent with prolonged flow, 6% had prolonged, infrequent with heavy bleeding. Non-structural (COEIN) causes contributed to about 60.4% of AUB in perimenopausal women and 39.6% had structural (PALM) causes. 49% cases were secretory endometrium. 29.3% had disordered proliferative endometrium, 4.3% had proliferative endometrium, 5.2% each had polyp or hyperplasia without atypia. 18 (15.5%) cases underwent hysterectomy, 3 patients who had adenocarcinoma underwent staging laparotomy, 2 patients had LNG IUS insertion and 40 patients were on follow up requiring either no treatment and 53 (45.68%) patients were given antifibrinolytics or hormonal therapy.Conclusions: Heavy and prolonged menstrual bleeding was the most common presenting symptom. COEIN contributed to about 60.4% of cases. Evaluation of the endometrium showed that, secretory endometrium was commonest (49%) followed by disordered proliferative endometrium (29.3%). On follow up for six months, 15.5% patients underwent hysterectomy, 2 patients had insertion of levonorgestrel IUD, 45.68% patients had medical management with antifibrinolytics or hormones and were on follow up. The responsibility of gynaecologist in the management of AUB in perimenopausal women is to exclude hyperplasia of endometrium and endometrial cancer.

Nuclear expression of VDR and AHR is mutually exclusive in glandular cells in endometriosis

The vitamin D receptor (VDR) and aryl hydrocarbon receptor (AHR) are two nuclear receptors that exert their effects by binding with ligands and forming a molecular complex. These complexes translocate to the nucleus and activate the expression of a series of genes which have a response element to VDR or AHR. Both receptors have been identified in the pathogenesis of endometriosis, a common disease characterized by the formation of endometrium-like tissue in ectopic zones. Despite numerous therapies, there is no definitive cure for endometriosis at the pharmacological level. Our study aims to describe the location and the expression of VDR and AHR at the protein level. For this purpose, an evaluation was performed using tissue from the three normal phases of the endometrium (proliferative, early, and late secretory) and in endometriosis by immunohistochemistry, using anti-VDR and anti-AHR antibodies. We demonstrate that in the nuclei of glandular cells in endometriosis, the expression of VDR and AHR is mutually exclusive—when the expression of one receptor is high, the other one is low—suggesting a possible target in the treatment of endometriosis. We also identify a significant change in the expression of glandular cytoplasmic AHR between the proliferative and late secretory endometrium.

Dydrogesterone is Superior as Luteal Phase Support in selected Previously Failed In-Vitro Fertilisation and Embryo Transfer Patients

Different forms of exogenous progesterone have been seen to play a very important role in endometrial maturity. Implantation failure appears to be a significant factor in Assisted reproductive technique (ART) procedures. Even a mature endometrium becomes non-receptive, preventing implantation or rejection of implanted embryo in early months of pregnancy. Hence natural micronized progesterone (NMP) and dydrogesterone have been used since decades to improve endometrial maturity and receptivity. The aim of this study was to investigate causes of failed implantation inspite of uneventful Grade I embryo transfer in ART procedure and the role of natural micronized progesterone (NMP) and dydrogesterone for endometrial maturation. 80 women aged range between 25-40 yr old who visited Department of Reproductive Medicine at Calcutta Fertility Mission, over a period of 24 months (January 2017 to December 2019), satisfying the inclusion criteria, were enrolled in this retrospective observational study. Endometrial aspirate histopathology was done during the secretory phase. They were treated with natural micronized progesterone (NMP) or oral dydrogesterone and results of endometrial changes, clinical pregnancy rate, live birth rate and miscarriage rate were statistically analysed. 26.25% and 29.6% of women were seen to have mid-secretory changes of the endometrium after being treated with NMP in one cycle and dydrogesterone in the subsequent cycle, respectively. 62.71% of women had shown early-secretory changes with dydrogesterone which was statistically significant compared to those treated with NMP (p value=0.006).8.5% of these women showed persistent non-secretory endometrium with either of these medications. The Clinical Pregnancy Rate (CPR) was 38.1% and 47% in the group of patients who were treated with NMP and dydrogesterone respectively. Though pregnancy rate was slightly higher in dydrogesterone group, it was not statistically significant (p value = 0.578). 28.5% and 41% women had live births and 9.5% and 5.8% of them had miscarriage in NMP and dydrogesterone group, respectively, though our data appears to be statistically not significant (p value –0.415) (p value – 0.679). In our study 26.25% women had mid-secretory endometrium after treatment with NMP. 29.6% and 62.71% of these women who had non-secretory or early secretory endometrial changes on treatment with intravaginal NMP, showed endometrial mid-secretory and early-secretory changes respectively, on treatment with dydrogesterone, which implies that oral dydrogesterone is superior to NMP when administered for endometrial maturation in selected patients. Clinical pregnancy rate, live birth rate or miscarriage rate were similar with either NMP or dydrogesterone.

Expression of Cyclin D1 in Hyperplasia and Carcinoma of Endometrium and Its Correlation with Histologic Grade, Tumor Type, and Clinicopathological Features

Background Endometrial carcinoma is often preceded by characteristic histopathologic lesions known as endometrial hyperplasia. Estrogen, p53, PTEN, and overexpression of cyclin D1 appear to be involved in the development of endometrial carcinogenesis. Design We evaluated and compared the expression profile of cyclin D1 expressions in 50 endometrial samples submitted as either endometrial curetting (n = 34) or hysterectomy (n = 16) specimens, which were diagnosed as simple hyperplasia (n = 10), complex hyperplasia (n = 06), atypical hyperplasia (n = 04), and endometrial carcinoma (n = 20). Ten cases of normal proliferative and secretory endometrium were selected as controls. Breast cancer with known cyclin D1 expression was selected as a positive control in each immunohistochemistry run. Results Cyclin D1 was significantly overexpressed in glands with complex hyperplasia and endometrial adenocarcinoma compared with proliferative or secretory endometrium and simple hyperplasia. A statistical difference was found in the extent of cyclin D1 positivity of simple hyperplasia and carcinoma of the endometrium (p < 0.005). No statistical difference was seen between complex hyperplasia and carcinoma and clinicopathologic parameters in endometrioid carcinomas. All cases of clear cell carcinoma and serous carcinoma showed cyclin D1 immunoreactivity. Significant statistical difference was seen between cyclin D1 expression and only one clinicopathologic parameter, i.e., menopausal status in endometrial carcinomas Conclusion Cyclin D1 over expression may be an early event in endometrial carcinogenesis and cyclin D1 over expression may be an informative biomarker to recognize subsets of endometrial lesions that may be precancerous and therefore amenable to surgical therapy.

Clinical and histopathological presentation of abnormal uterine bleeding in perimenopausal women in tertiary center of Nepal

Background: Abnormal uterine bleeding is defined as any bleeding outside of normal menstruation pattern with excessive duration, frequency, and amount and it is a common problem among women of reproductive age group with varied presentations. The aim of the study was to correlate the histopathological finding in patients with abnormal dysfunctional uterine bleeding with the presenting clinical feature.Methods: A prospective cross sectional study was carried out at Paropakar Maternity and Women’s Hospital, Thapathali, Kathmandu during the period of one year (February 2019 to January 2020). It included 77 perimenopausal women with abnormal uterine bleeding who presented in gynecology outpatient department and planned for dilatation and curettage. Then the participants were counselled and informed consent was taken. Histopathological reports reviewed and analysis done. Results: The most common age group of women presenting with abnormal uterine bleeding was 40 to 44 years and the commonest clinical feature was menorrhagia (31/77, 40.3%) followed by menometrorrhagia (18/77, 23.4%). Majority of women were multiparous, parity 3 to 4 (38/77, 49.4%). Proliferative endometrium (29/77, 37.7%) was most common histopathological findings followed by secretory endometrium (24/77, 31.2%). Proliferative endometrium was more commonly associated with menorrhagia and menometrorrhagia whereas secretory endometrium with metrorrhagia (P-value 0.000).Conclusions: Menorrhagia and Menometrorrhagia are the most common clinical presentation among perimenopausal women with AUB, whereas proliferative endometrium and secretory endometrium were the common histopathological findings respectively.Accurate diagnosis is crucial for a selection of relevant treatment and avoidance of unnecessary major surgical procedure. Keywords: Abnormal uterine bleeding; endometrium; histopathology; perimenopausal.

Review of histopathologic findings of endometrial biopsy done at a tertiary referral hospital in urban Ethiopia

BackgroundAn endometrial sampling procedure is a gold standard for the diagnostic evaluation of women with abnormal uterine bleeding (AUB) with primary aim to identify the cause, especially to determine whether carcinoma or premalignant lesions are present. The objective of the study is therefore to review endometrial biopsy specimen histopathological findings and associated factors at a tertiary referral hospital in urban Ethiopia.MethodologyThis is a two years retrospective analysis of cases of patients for whom endometrial biopsy was taken at a territory referral hospital in urban Ethiopia. Odd’s ratios, 95% confidence interval and p-value set at 0.05 were used to determine the statistical significance of the associations.ResultsA total of 277 patient records were analyzed and mean and the median age of the study patients were 41.89 and 40.00 years respectively. The commonest histopathologic finding was endometrial polyp 66 (23.83%), followed by proliferative endometrium 47 (16.97%) and secretory endometrium 25(9.03%). Endometrial hyperplasia, endometrial malignancy, and pregnancy complications were reported in 9 (3.25%), 13 (4.69%), and 25 (9.03%) of cases respectively. Endometritis was detected in 20(7.22%), while Tuberculous (TB) endometritis was reported in 3(1.08%) of cases only. Inconclusive and inadequate sample was reported in 30 (10.83%) and 34 (12.27%) of cases respectively. Endometrial polyp was associated with 40-49 years of age (OR= 12.56, 95% CI: 2.58-61.23).ConclusionsEndometrial polyp was the commonest histopathologic finding followed by proliferative and secretory endometrium respectively. Rate of sample inadequacy is higher than most of the study reports which mandates to improve sampling technique to increase sample adequacy and routine transvaginal ultrasound for endometrial evaluation especially for those postmenopausal women to decide the necessity of endometrial sampling.

Endometrial assessment in cases of primary infertility in women: a prospective study

Background: Worldwide Infertility rate prevails around 8-12% of all couples; approximately 80 million are infertile. In India 10-15% of couples are infertile. Investigating for infertility is to intervene into the modifiable/treatable causes. Therefore, the present study has been undertaken to investigate the morphological patterns of endometrial tissue in women with primary infertility.Methods: The study included 60 cases with complaints of infertility (primary). The premenstrual D and C was done to obtain endometrial biopsy. The present prospective study was a descriptive study and the values are mentioned in percentages.Results: In present study a total of 60 cases were studied. Out of which 36 cases (60%) belonged to the young adult age group. The predominant morphological pattern was that of secretory endometrium seen in 22 cases (36.66%) as opposed to proliferative, endometritic or tubercular pattern. The predominant menstrual pattern recorded was regular; seen in 41 cases (68.33%) as opposed to irregular or mennorhagic patterns.Conclusions: The endometrial biopsy has a great role in screening the cases of infertility as it helps to assess the information about ovulation, ripening of the endometrial tissue and other abnormal endometrial reaction, hormonal imbalance. This is the only method to label the diagnosis of endometrial tuberculosis in an apparently healthy female.

Uterine fluid proteins for minimally invasive assessment of endometrial receptivity

Context Clinically used endometrial (EM) receptivity assays are based on transcriptomic patterning of biopsies at mid-secretory endometrium (MSE) to identify the possible displacement or disruption of window of implantation (WOI) in patients with recurrent implantation failure (RIF). However, biopsies are invasive and cannot be performed in the same cycle with IVF embryo transfer, while uterine fluid (UF) analysis is considered minimally invasive and can immediately precede embryo transfer. Objective To determine whether UF proteome can be used for WOI monitoring and whether it would highlight the etiology of RIF. Patients Paired early secretory endometrial (ESE) and MSE UF samples from six fertile control women for discovery, and additional 11 paired ESE/MSE samples from controls and 29 MSE samples from RIF patients for validation. Results Using discovery mass spectrometry (MS) proteomics we detected 3,158 proteins from secretory phase UF of which 367 undergo significant (q < 0.05) proteomic changes while transitioning from ESE to MSE. 45 proteins were further validated with targeted MS, and 21 were found to display similar levels between control ESE and RIF MSE, indicating displacement of the WOI. Panel of PGR, NNMT, SLC26A2 and LCN2 demonstrated specificity and sensitivity of 91.7% for distinguishing MSE from ESE samples. The same panel distinguished control MSE samples from RIF MSE with a 91.7% specificity and 96.6% sensitivity. Conclusion UF proteins can be used for estimating uterine receptivity with minimal invasiveness. Women with RIF appear to have altered MSE UF profiles that may contribute to their low IVF success rate.