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Purpose: The aim of this study was to evaluate whether the number of p16-positive cells in the functional layer of the endometrium could be a useful biomarker to identify women with recurrent implantation failure (RIF) undergoing in vitro fertilization (IVF) at risk of miscarriage., Methods: Immunohistochemical staining was performed in 311 endometrial biopsies taken during mid-luteal phase using antibody against p16 INK4A . The percentage of p16-positive cells was determined in luminal, glandular and stromal endometrial cells. After embryo transfer, women were divided into the following groups: unsuccessful embryo implantation (n = 151), miscarriage (n = 66) and live birth (n = 94). The percentage of p16-positive cells in all endometrial compartments was compared among these groups., Results: We found that the percentages of p16-positive glandular and luminal epithelial endometrial cells were significantly higher in patients with live births compared to women with miscarriage (9.3% vs. 2.9%, P < 0.001; and 35.2% vs. 11.7%, P = 0.001, respectively). This tendency was not confirmed in thе stroma. The cut-off values with p16-positive luminal cells lower than 12.5% and p16-positive glandular cells lower than 3.2% could be predictive factors for miscarriage (AUC 0.80 and 0.79; sensitivity 71.3% and 74.5%; specificity 74.2% and 71.2%, respectively)., Conclusion: A decreased number of senescent p16-positive cells could be involved in the implantation failures and aetiology of recurrent miscarriage. Women with history of RIF with reduced populations of p16-positive cells in the endometrial glandular and luminal epithelium may be at greater risk for unsuccessful implantation and miscarriage. The percentage of p16-positive luminal epithelial cells may be clinically useful as a biomarker of miscarriage., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries.DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood., Methods: We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions., Results: Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles.SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders., Conclusion: Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis.

Intrauterine insemination (IUI) is a method for the treatment of marital infertility involving the intrauterine or fallopian deposition of washed spermatozoa, depending on the amount of inseminated semen. Numerous factors may be affect of pregnancy rates after IUI.

In the first part of publication the authors make a profound review of history of development and qualities of Intra Uterine Devices/IUD's/. There are reflected the first steps dated from the ancient times to come to modern IUD's (Multiload, Copper T. Slimline). In Table 1 and 2 (on W.A.A. van Os) are represented single cases (pregnancy, expulsion and extracted IUD's) related to the modern intrauterine devices: MLCu 250 and MLCu 375 for the periods of 1, 3 and 5 years. In the second part the authors represent their scientific and practical results which has been obtained at the Bulgarian Family Planning and Sexual Health Association and the Ob./Gyn. Department of Medical University-Sofia. A retrospective research has been conducted on 406 women who delivered between 18 and 42 years of age and to which MLCu 375 have been inserted. The so analyzed and presented results show very good qualities of MLCu 375 IUD. The cases' frequency corresponds to the one announced by the world leading practice of contraception.