Short-term reproductive outcomes analysis and prediction of the modified uterine stent treatment for mild to moderate intrauterine adhesions: experience at a single institution.

BACKGROUND: To evaluate the efficacy of modified uterine stent in the treatment of mild-to-moderate intrauterine adhesions and explore the relative indicators affecting prognosis prediction. METHODS: A total of 115 patients with mild-to-moderate intrauterine adhesions received a modified uterine stent placement after hysteroscopy adhesiolysis. The second-look hysteroscopy operated after 3 months surgery, and the third-look hysteroscopy operated after 6 months surgery if necessary. The stent was removed when the cavity shape was repaired, then the reproductive outcomes were followed up one year. RESULTS: Menstrual blood volume, endometrial thickness and volume had increased significantly after 3 months surgery. The rates of cavity repaired were 86.96% (100/115) after 3 months surgery and 100% (115/115) after 6 months surgery cumulatively. Endometrial thickness after 3-months surgery was positively associated with uterine cavity shape repaired (P<0.01). The receive operating characteristic (ROC) curve showed the rate of uterine cavity shape repaired predicted by the model was 0.92, based on the endometrial thickness after 3-months surgery. The rate of pregnancy was 86.09% (99/115) in one year, while the rate of miscarriage accounted for 26.26% (26/99). The median time interval between stent removal and subsequent conception was 3 months. It showed adhesion recurrence was the risk factor for subsequent pregnancy (P<0.01). CONCLUSIONS: A modified uterine stent placement under hysteroscopy was an effective approach for mild-to-moderate intrauterine adhesions, which is easy to operate and worthy for clinical promotion. Endometrial thickness measured by ultrasonography probably has predictive value in adhesion recurrence and subsequent pregnancy. TRIAL REGISTRATION: ChiCTR2100051524. Date of registration (retrospectively registered): 26/09/2021.

A retrospective study of estrogen in the pretreatment for medical management of early pregnancy loss and the inference from intrauterine adhesion.

BACKGROUND: Estrogen has been usually used in clinic for medical pretreatment of early pregnancy loss. There was little reported the effect of estrogen combined with prostaglandin analogs in the medical management of early pregnancy loss. This retrospective study aimed to evaluate the efficacy of estrogen pretreatment for medical management of early pregnancy loss and explore the confounding factor of intrauterine adhesion (IUA) on the outcome of medical management. METHODS: A total of 226 early pregnancy loss patients who received pretreatment with estradiol valerate and/or mifepristone, followed by carboprost methylate suppositories (study groups), or carboprost methylate suppositories alone (control group) in a regional central institution from March 2020 to February 2021 were retrospectively studied. All patients were evaluated by hysteroscopy 6 h after carboprost methylate suppositories use to assess whether the gestational sac was complete expulsion and assess the morphology of uterine cavity. RESULTS: The complete expulsion rate was 56.94% in the mifepristone and estradiol valerate-pretreatment group, 20.69% in the estradiol valerate-pretreatment group, 62.5% in the mifepristone-pretreatment group, and 12.5% in the control group. Compared with the control group, pretreatment with estradiol valerate did not increase the complete expulsion rate significantly (P = 0.297), pretreatment with mifepristone increased the complete expulsion rate significantly (P < 0.001). Pretreatment with mifepristone combined with estradiol valerate did not increase the complete expulsion rate significantly comparing with pretreatment with mifepristone (P = 0.222). The data of IUA showed that the complete expulsion rate in patients with IUA was lower than that in those patients without IUA (P < 0.001). CONCLUSIONS: Pretreatment with estrogen was not a sensible substitute for mifepristone in the medical management of early pregnancy loss. Mifepristone followed by carboprost methylate suppositories was likelihood of the ideal medical scheme in early pregnancy loss. IUA decreased the complete expulsion rate of medical management, it is cautious about medical management for early pregnancy loss with risk of IUA. TRIAL REGISTRATION NUMBER: ChiCTR2100046503. Date of registration (retrospectively registered): May 18, 2021. Trial registration website: http://www.chictr.org.cn/ .

IL6 Induces mtDNA Leakage to Affect the Immune Escape of Endometrial Carcinoma via cGAS-STING.

Endometrial carcinoma (EC) is a commonly diagnosed gynecological malignancy. Interleukin-6 (IL6) plays a critical role in modulating the progression of several types of tumors, including EC. However, the specific mechanism of IL6 in regulating EC progression has not been clearly elucidated. In this study, we performed a series of functional experiments to explore the potential mechanisms involved in IL6 function in the progression of EC. Here, we found that IL6 increased reactive oxygen species (ROS) generation by enhancing the NADPH oxidase (NOX) level and induced mtDNA leakage in EC cells, which further caused the activation of the downstream cGAS-STING signaling and increased production of extracellular vesicle (EV) production from EC cells. Besides, the activation of cGAS-STING signaling enhanced the expression of type I IFN and its downstream molecule PD-L1 through the TBK1-IRF3 pathway. Importantly, a high level mtDNA and PD-L1 were present in EVs derived from IL6-induced EC cells; these vesicles were shown to be able to induce T cell apoptosis. Finally, anti-PD-L1 treatment in mice showed that blockade of PD-L1 significantly reversed tumor immune escape mediated by IL6-induced EVs. Together, we provide evidence that IL6 induced mtDNA leakage to regulate the immune escape of EC cells. Our findings may provide a novel clue for the development of therapeutic targets for EC.

The Immune Atlas of Human Deciduas With Unexplained Recurrent Pregnancy Loss.

Recurrent pregnancy loss (RPL) is a common fertility problem that affects 1%-2% of couples all over the world. Despite exciting discoveries regarding the important roles of the decidual natural killer cell (dNK) and regulatory T cell in pregnancy, the immune heterogeneity in patients with unexplained recurrent pregnancy loss (URPL) remains elusive. Here, we profiled the transcriptomes of 13,953 CD45+ cells from three normal and three URPL deciduas. Based on our data, the cellular composition revealed three major populations of immune cells including dNK cell, T cell, and macrophage, and four minor populations including monocytes, dendritic cell (DC), mast cell, and B cell. Especially, we identified a subpopulation of CSF1+ CD59+ KIRs-expressing dNK cells in normal deciduas, while the proportion of this subpopulation was decreased in URPL deciduas. We also identified a small subpopulation of activated dDCs that were accumulated mainly in URPL deciduas. Furthermore, our data revealed that in decidua at early pregnancy, CD8+ T cells exhibited cytotoxic properties. The decidual macrophages expressed high levels of both M1 and M2 feature genes, which made them unique to the conventional M1/M2 classification. Our single-cell data revealed the immune heterogeneity in decidua and the potentially pathogenic immune variations in URPL.