The effects of dienogest and combined oral contraceptives on protein S-specific activity in endometriosis patients.

OBJECTIVE: One serious side effect of combined oral contraceptives (COCs) is venous thromboembolism. Reduced activity in activated protein C-related coagulation pathways is attributable to low protein S activity in one-third of Japanese patients with deep vein thrombosis. Herer, we quantified the behavior of protein S-specific activity in response to dienogest (DNG) and COCs using the protein S-specific activity assay system to explore its potential utility as a thrombosis marker. STUDY DESIGN: This was a prospective cohort study. Female patients aged 20 - 49 years who were starting drug treatment for endometriosis using DNG or COCs were enrolled. Blood samples were taken before treatment and at the first, third, and sixth months of treatment. To analyze the primary endpoints, changes in total protein S antigen levels, total protein S activity, and protein S-specific activity from baseline to each time point were estimated using a linear mixed-effects model. All statistical analyses were performed in the SAS software version 9.4 (SAS Institute, Cary, NC). A two-sided P < 0.05 was considered statistically significant. RESULTS: 64 patients took DNG and 34 patients took COCs. Protein S-specific activity did not change significantly from baseline in the six months after treatment started in either group. In the DNG group, total protein S activity and total protein S antigen levels increased slightly from baseline levels after the treatment. The means for total protein S activity and total protein S antigen levels in the COC group remained within reference limits, but they both decreased markedly in the first month and stayed low. Protein S-specific activity in four women remaind below the reference limit throughout the whole study period, suggesting they may have potential protein S deficiencies. CONCLUSION: The effects of DNG on protein S were negligible, though both total protein S activity and antigen levels decreased soon after COC treatment began and remained low. As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk.

Identification of genes associated with endometrial cell ageing.

Ageing of the uterine endometrium is a critical factor that affects reproductive success, but the mechanisms associated with uterine ageing are unclear. In this study, we conducted a qualitative examination of age-related changes in endometrial tissues and identified candidate genes as markers for uterine ageing. Gene expression patterns were assessed by two RNA-sequencing experiments using uterine tissues from wild type (WT) C57BL/6 mice. Gene expression data obtained by RNA-sequencing were validated by real-time PCR. Genes expressing the pro-inflammatory cytokines Il17rb and chemokines Cxcl12 and Cxcl14 showed differential expression between aged WT mice and a group of mice composed of 5- and 8-week-old WT (young) animals. Protein expression levels of the above-mentioned genes and of IL8, which functions downstream of IL17RB, were analysed by quantitative immunohistochemistry of unaffected human endometrium tissue samples from patients in their 20s and 40s (10 cases each). In the secretory phase samples, 3,3'- diaminobenzidine staining intensities of IL17RB, CXCL12 and CXCL14 for patients in their 40s were significantly higher than that for patients in their 20s, as detected by a Mann-hitney U test. These results suggest that these genes are candidate markers for endometrial ageing and for prediction of age-related infertility, although confirmation of these findings is needed in larger studies involving fertile and infertile women.

Infertility after abdominal trachelectomy.

INTRODUCTION: Despite numerous reports on pregnancy outcomes after trachelectomy, there are few descriptions of fertility treatment after trachelectomy. Moreover, little is known about the differences in fertility outcomes between various radical trachelectomy procedures. The purpose of this report was to clarify the infertility problems that occur in patients who have previously undergone an abdominal trachelectomy. MATERIAL AND METHODS: We retrospectively investigated the medical records of 37 patients who received fertility treatments or were evaluated for menstrual disorders after trachelectomies in our institution between 2012 and 2016. RESULTS: Twenty-two of 37 patients had complications which affected fecundity. Six patients had cervical stenosis requiring surgical dilation, 4 had ovarian insufficiency, and 14 had Asherman's syndrome. CONCLUSIONS: In spite of efforts to preserve fertility, some patients have severe complications after trachelectomy, such as Asherman's syndrome, resulting in infertility. Clinicians should pay careful attention to the status of the endometrial cavity after trachelectomy.