Three-year observational study of immediate post-abortion insertion versus menstrual insertion of etonogestrel contraceptive implant.

OBJECTIVE: This study aimed to estimate the difference in vaginal bleeding pattern, discontinuation rate, and satisfaction between immediate after abortion and menstrual insertions of etonogestrel contraceptive implants. STUDY DESIGN: Between May 2013 and November 2015, 66 women were recruited in the abortion group who selected etonogestrel implants as their contraceptive immediately after induced abortion. 84 women who underwent the placement of the etonogestrel implant during their menstrual period were enrolled as the menstrual group. The two groups participated in 3-year follow-up outpatient visits at 1, 6, 12, 24, and 36 months after implantation. The vaginal bleeding pattern, discontinuation rate, satisfaction rate were recorded and compared. RESULTS: No woman had pregnancy over the study period of 3 years. The incidence of amenorrhea/infrequent bleeding did not differ between the two groups after 12, 24, and 36 months of implantation (53.0% vs. 58.4%, 47.8% vs. 51.6%, and 48.6% vs. 55.6%, respectively). In the abortion group, the incidences of frequent/prolonged bleeding were 15.1%, 32.6%, and 27.0% after 12, 24, and 36 months of implantation, respectively, while the other group showed 27.3%, 25.8%, and 20.4%, respectively. After 12 and 24 months, the continuation use rates were 69.7% and 56.1% in the abortion group and 73.8% and 64.2% in the menstrual group. The 12-month satisfaction rate between abortion group and menstrual group was 69.6% versus 72.6%. Statistical analyses show that there was no difference in vaginal bleeding pattern, discontinuation rate or satisfaction between the two groups. CONCLUSIONS: Immediately post-abortion may be also a favorable time to undergo etonogestrel implantation.

The feasibility of laparoscopically assisted, hysteroscopic removal of interstitial pregnancies: A case series.

OBJECTIVE: The study objective was to assess the feasibility of the management of interstitial pregnancy by laparoscopically assisted hysteroscopic removal. METHODS: This retrospective study included a case series of 17 patients who were diagnosed interstitial pregnancy with dilated proximal tubal ostium by transvaginal ultrasonography at the Women's hospital, School of Medicine, Zhejiang University between August 2017 and October 2020. Laparoscopically assisted hysteroscopic removals of the products of conception were performed. Various data were collected including age, surgical and obstetric history, gestational age, preoperative symptoms, human chorionic gonadotropin level and ultrasonography results. The outcomes measured were intraoperative bleeding, pathologic findings, conversions. RESULTS: Eleven cases were successfully resected the interstitial gestational products with laparoscopically assisted hysteroscopy. There were four cases failed of hysteroscopic removal, for the proximal tubal ostia were too small for the surgical instruments to enter. Then cornual wedge resections were performed. Two cases were identified as intramural pregnancy by hysteroscopic and laparoscopic view. Most of the intramural pregnancy tissue of one patient was removed by hysteroscopy. The other one converted to laparoscopy. CONCLUSION: Laparoscopically assisted hysteroscopic management could be a feasible surgical option to interstitial pregnancies. Further clinical studies are needed to establish detailed criteria to select the appropriate cases for hysteroscopic management.

Mifepristone regulates Tregs function mediated by dendritic cells through suppressing the expression of TGF-ß.

BACKGROUND: Previous studies have demonstrated that mifepristone in the daily low-dose affects the function of endometrium. These researches also implied an alteration of endometrium immune balance, which might be involved in regulating endometrial function. However, the detailed mechanisms remain to be further explored. METHODS: In this study, the expressions of CD80, CD86, and ICAM-1 in dendritic cells (DCs), which were stimulated with different concentrations of mifepristone (20, 65, and 200 nM), were detected by FACS. After that, we further evaluated the expression of Forkhead box P3 (FOXP3) and IL-10 in Tregs, which co-cultured with mifepristone treated DCs. In mechanism, we compared the indoleamine 2,3-dioxygenase (IDO) and TGF-ß expression with enzyme-linked immunosorbent assay (ELISA). RESULTS: The results indicated that mifepristone promoted the expressions of CD80, CD86, and ICAM-1 in a dosage dependent manner. Reversely, FOXP3 and IL-10 expression levels in Tregs co-cultured with mifepristone-treated DCs were significantly decreased compared with those co-cultured with nontreated DC. Furthermore, a significant reduce in IDO and TGF-ß expression was observed in DCs treated with mifepristone. By using the IDO inhibitor (1-methyl tryptophan, 1-MT) or TGF-b supplement, we confirmed that TGF-ß, but not IDO could rescue the downregulation of FOXP3 and IL-10 in Tregs co-cultured with mifepristone treated DCs. All of these results suggest that mifepristone may regulate DC function by decreasing TGF-ß expression, which further results in the downregulations of FOXP3 and IL-10 in Tregs. CONCLUSION: Therefore, our research provides a theoretical basis for a potentially clinical application of mifepristone as a novel contraceptive.

SIRT4 Has an Anti-Cancer Role in Cervical Cancer by Inhibiting Glutamine Metabolism via the MEK/ERK/C-Myc Axis.

BACKGROUND/AIM: Glutamine metabolism is crucial in cell proliferation, aging, and apoptosis across various cancer types. Existing research indicates that Sirtuin 4 (SIRT4), primarily located in mitochondria, modulates this process. This study aimed to clarify the regulatory relationship between SIRT4 and glutamine metabolism in cervical cancer. MATERIALS AND METHODS: SIRT4 mRNA levels and their clinical correlation to cervical cancer were analyzed using the UALCAN database. Immunohistochemistry (IHC) was performed to assess SIRT4 protein expression in tissue samples from cervical cancer patients. Transient transfection was employed to create Hela and Siha cell lines with overexpressed SIRT4, mitogen-activated extracellular signal-regulated kinase (MEK), and glutaminase 1 (GLS1). The impact on cellular functions was studied using MTT, soft agar, transwell, and western blotting assays. Glutamate and ATP levels were also measured to evaluate metabolic changes. RESULTS: Low levels of SIRT4 mRNA in cervical cancer tissues correlated with tumor metastasis and poor survival rates. Overexpression of SIRT4 led to suppressed cell proliferation, colony growth, and motility, along with significant down-regulation of GLS expression, a key contributor to glutamine metabolism. Additionally, SIRT4 overexpression resulted in the inactivation of the MEK/ERK/c-myc signaling pathway, while overexpression of MEK reversed these effects. Notably, the inhibitory effects of SIRT4 on cell proliferation, colony formation, migration, and invasion in Hela and Siha cells were significantly attenuated following GLS1 overexpression. CONCLUSION: SIRT4 acts as an anti-cancer agent in cervical cancer by inhibiting glutamine metabolism through the MEK/ERK/c-myc signaling pathway, providing a novel sight for cervical cancer therapy.

Mifepristone regulates macrophage-mediated natural killer cells function in decidua.

Mifepristone has been used for first-trimester abortion and contraception. Nevertheless, its functional mechanism still needs to be elucidated. Decidua tissues were collected from 40 pregnant women who received (20 patients) or did not receive (20 patients) mifepristone. Immunofluorescence was used to analyze the effect of mifepristone on the quantity of CD56 and CD206 in decidua. in vitro assay, NK cells were isolated from decidua tissue and macrophages were induced from THP-1 cells. NK cells were co-cultured with macrophages pre-treated different concentrations of mifepristone (0 nmol/L, 200 nmol/L, 1800 nmol/L, and 25000 nmol/L); the cells' cytotoxicity and migration ability were analyzed using MTT assay and transwell assay, respectively. Si-TGF-ß1, which was utilized to knock down the TGF-ß1 expression in macrophages and human recombinant TGF-ß1 were used to verify whether TGF-ß1 was involved in the mifepristone regulation of NK cells function. The quantity of CD56 and CD206 decreased after mifepristone treatment. Moreover, the NK cells' cytotoxicity and migration ability were significantly increased by macrophages pre-treated with mifepristone in a dose-dependent manner. Moreover, compared with the si-NC group, the MTT absorbance rate of NK cells was significantly increased in the si-TGF-ß1 group and was decreased in the human recombinant TGF-ß1 group. Our data suggest that mifepristone, which regulates NK cells function through macrophages, was associated with the changes in TGF-ß1 secreted by macrophages. This may be one of the mechanisms of mifepristone acting as contraceptive and abortion drugs at the maternal-fetal interface.

Effects of Etonogestrel implants on pelvic pain and menstrual flow in women suffering from adenomyosis or endometriosis: Results from a prospective, observational study.

ABSTRACT: Adenomyosis and endometriosis are common causes of pelvic pain in women of reproductive age. Furthermore, adenomyosis is a major cause of menorrhagia. This study aimed to evaluate the effects of Etonogestrel implants on pelvic pain and menstrual flow in women requiring long-acting reversible contraception and suffering from adenomyosis or endometriosis.One hundred women with adenomyosis or endometriosis and asking for contraception with Etonogestrel implants were enrolled in this study and were followed-up for 24 months. Patients were interviewed on pelvic pain by visual analog scale (VAS) pain score, menstrual flow by the number of sanitary napkins, menstrual bleeding pattern, weight gain, breast pain, and any other treatment side effects.Seventy four patients who were treated with Etonogestrel implants completed the 24-month follow-up in which we found a significant decrease in pelvic pain VAS scores comparing baseline scores to 6, 12, and 24 months (baseline: 6.39 ±â€Š2.35 to 24-month: 0.17 ±â€Š0.69, P < 0.05). The menstrual volume decreased significantly compared with that at baseline ((40.69 ±â€Š30.92) %, P < 0.05). However, vaginal bleeding, amenorrhea, weight gain, and acne occurred after treatment in some patients.Etonogestrel implants were effective in reducing pelvic pain and menstrual flow of adenomyosis or endometriosis.