Research aim: to investigate the proliferative status of endometrium in the different morphotypes of endometrial hyperplasia based upon the identification of key molecular markers of the cell cycle.Materials and methods. Endometrial samples taken from 137 women were investigated: 40 – normal endometrium (NE), 61 – non-atypical endometrial hyperplasia (ЕH), 36 – atypical hyperplasia (AHE). Expression of gene cyclin D1, nuclear antigen Кі-67, glycoproteins Е-cadherin and β-catenin, estradiol receptors (ER) and progesterone receptors (PGR) were investigated. Results. ER expression of NE was high in the proliferative phase and decreased significantly in the secretory phase. PGR expression was high in both phases. ER expression of EH in glandular (180 ± 8.3) and in stromal cells (170.5 ± 4.1) exceed the indicators of the secretory phase. PGR expression in the stromal cells of EH (197.5 ± 9.3) exceed significantly indicators of NE. ER and PGR expression significantly and reliably decreased if there was AHE. ER expression of glandular cells was 2.6 times lower (74.6 ± 3.9) compere to proliferative NE (p <0.05) and 2.4 times lower to EH (р <0.05). ER of stromal AHE cells dropped to 30.3 ± 2.8, which was 5.5–5.6 times lower than in the proliferative NE and EH (p <0.002). PGR expression was 2.5–2.7 times lower (71.1 ± 2.3) in AHE glands than in NE and 2.8 times lower than in EH (p <0.05). Gene cyclin D1 expression was reliably increased in AHE cells compere to NE and EH. Protein Кі-67 expression in the glandular cells of EH was 2.6 times lower (p <0.05) and in AHE 2.9 times lower (p <0.05) than NE proliferative phase. We discovered strong direction to decreasing Е-cadherin expression in EH and it was lowest for AHE. Opposite direction was expression of β-catenin. The highest numbers of positive samples were observed in AHE and it was 100%. The highest numbers of negative β-catenin samples were in the NE cells (32,5–35%).Conclusion. The epigenetic profile investigation of endometrial hyperplasia will be useful for future development of carcinogenesis risk stratification, identifying patients with high risk of endometrial cancer and also for choosing the optimal way to influence the pathological process in the endometrium.

Introduction. Endometrial hyperplasia is a commonproblem among premenopausal women. There are nonatypical (EH) and atypical (AH) morphotypes according tocytological atypia. Despite a mostly favorable prognosisof EH, risk of progression to atypia is nearly 2% per year.The next problem is absence of clear criteria on which casewill have an unfavorable prognosis and EH will progress toAH and endometrial cancer. Markers of response of EH andAH to the first line therapy such as progestin are not wellinvestigated either. Investigation of ER and PGR expressionin normal (NE) and hyperplastic endometrium can be usefulfor future development of treatment algorithms in differentendometrial hyperplasia morphotypes and forecastingresponses to progestin therapy.Objective: To investigate the expression of estradiol andprogesterone receptors in the glandular and stromal cells ofnormal endometrium and in the different morphotypes ofendometrial hyperplasia.Material and Methods: Endometrial samples taken from137 women were investigated: 40 – with normal proliferativeand secretory endometrium (NE), 61 – endometrialhyperplasia without atypia (ЕH), 36 – endometrialhyperplasia with atypia (AH). Routine histopathologicaland immunohistochemical (IHC) examination of nuclearantigens in the endometrium samples was conducted. Then,IHC examination was carried out on the paraffin blocksusing monoclonal and polyclonal antibodies and systems ofvisualization. Expression of estradiol (ER) and progesterone(PGR) receptors was investigated. Taking into account thatcells with positive reaction to ER and PGR have significantdifferences in the intensity of IHC coloring, we used theaverage value or H-index according to the number of cellswith positive reaction and reaction intensity. Values from0 to 50 on the H-index were considered for the absence ofER and PGR expression, from 50 to 100 - expression ofantigens to receptors was considered as weakly positive;100 points or more - as positive. Statistical processing ofresults was done using licensed program Statistics (V 6.1;Statsoft, USA).Results: ER expression of EH both in glandular cells (180±8.3) and stromal cells (170.5±4.1) was close to resultsof proliferative NE (193.1±12.2 in the glandular and 166±9.7in the stromal cells), but 1,43 times exceeded indicators inthe glandular (180±8.3 vs 125.4±5.7; p<0.05) and 1.9 timesin the stromal cells (170.±4. vs 122.±4.; p<0.5) of secretoryNE. PGR expression in the glandular cells of EH wasalmost the same as this indicator of NE. PGR expressionin the stromal cells of EH was 197.±9.3 points and it wassignificantly higher compared to NE. On the contrary, withAHE ER and PGR expression significantly and reliablydecreased. ER expression of glandular cells (74.6±3.9points) was 2.6 times lower compared to proliferative NE(p<0.05) and 2.4 times lower to EH (р<0.05). ER of stromalAHE cells dropped to 30.3±2.8, which was 5.5 times lowerthan in NE of the proliferative phase (p<0.002) and 5.6times lower than in EH (p<0.002). PGR expression had thesame direction and also decreased. AHE glandular PGRexpression (71.1±2.3) was 2.7-2.5 times lower than thisindicator in the proliferative and secretory NE respectively(p<0.05). Reliable differences in PGR expression betweenAHE and EH were found. Glandular PGR expression indexAHE was 2.8 times lower than the same EH indicator(p<0.05), stromal one was 2.4 times lower (p<0.05).Conclusion: Estradiol and progesterone receptors dataof endometrium will be useful for future developmentof carcinogenesis risk stratification at the early stage,identifying patients with high risk of endometrial cancerand also for choosing the optimal way to influence thepathological process in the endometrium.

Recurrent pregnancy loss (RPL) is a polyetiological pathology, with the majority of causes and risk factors still not fully understood. The paper provides an overview of the current clinical guidelines on RPL, which shows the contradictions of recommendations for certain positions of examination and treatment. Taking into account the differences in the recommendations for genetic testing a detailed review of primary sources on the contribution of chromosomal pathology to RPL was done that confirms the value of cytogenetic testing of the conception product and need for attention to study of other than mother’s age factors that increase the risk of recurrent quantitative chromosomal abnormalities (aneuploidies, polyploidies). Balanced structural chromosomal abnormalities are the cause 5% of RPL. Carriers of balanced structural abnormalities do not phenotypically differ from people with a normal karyotype, but have a high risk of infertility, recurrent miscarriage, stillbirth, and birth of a child with chromosomal abnormalities. Examination of spouses with RPL for balanced structural chromosome abnormalities is the first and mandatory stage of examination, especially if cytogenetic examination of the conception products was not performed or was not informative.This article also includes a review of studies in 2019–2020 years on improving diagnostic algorithms for the RPL causes to reduce the idiopathic cases. Scientific researches prove that a complete examination to identify all possible causes of RPL regardless of the result of the conception product karyotype determining can reduce the frequency of idiopathic RPL to 10–15%.Thus, the exhaustive examination of all couples with RPL (diagnosis of genetic, anatomical, autoimmune, hormonal and microbiological causes, as well as a thorough assessment of risk factors) can significantly reduce the proportion of idiopathic forms of RPL. This reduces the stress of uncertainty and unreasonable empirical treatment in patients and provides a possibility to develop an individual plan for reproduction, using assisted reproductive technologies if necessary.

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