UNASSIGNED: Endometriosis is a chronic inflammatory gynecological disorder that causes pelvic pain. Due to the heterogeneity of the disease, response to any treatment in an individual is variable. We aimed to develop in vitro testing that could be adapted for use in precision therapy for endometriosis. We piloted a personalized medicine approach by identifying predictive biomarkers while determining the effect of bazedoxifene (BZA) and medroxyprogesterone acetate (MPA) on the gene expression of a progesterone receptor (PR), an estrogen receptor (ER), and an aromatase (CYP19A1) enzyme in cells cultured from biopsies of endometriosis patients. The differential expression of the most common molecular targets in endometriosis therapy correlated with cellular response.
UNASSIGNED: Primary eutopic endometrial stromal cells were cultured from endometrial biopsies obtained in secretory phase from women between 24 and 42 years old with moderate-to-severe endometriosis (stages III and IV). Exclusion criteria included use of hormonal treatments and intrauterine contraception in the 6 months prior to surgery. Cells were treated either with BZA, MPA, or vehicle control. Total RNA was extracted from the treated and untreated cells. Differential expression of genes that are involved in the pathogenesis of endometriosis was determined by quantitative reverse transcriptase-polymerase chain reaction analysis.
UNASSIGNED: After determining the baseline expression levels of PRA/B, ERα and CYP19A1, response to treatment was monitored using Ki-67 as a marker of cell proliferation. MPA was effective in blocking proliferation in the group expressing high levels of PRA/B. Endometrium expressing high levels of CYP19A1 preferentially responded to BZA, a selective estrogen receptor modulator known to block estrogen action in endometrium.
UNASSIGNED: PR expression may predict progestin resistance in endometriosis while CYP19A1 expression may indicate the need to block estrogen signaling.

This study aimed to improve the knowledge of low-grade endometrial stromal sarcoma (LG-ESS) with intracaval or intracardiac extension and tried to identify the potential risk factors and optimal treatment method influencing prognosis.
We performed a retrospective review of eight LG-ESS patients with intracaval or intracardiac extension who underwent treatment at Peking Union Medical College Hospital between 2012 and 2020.
The median age at diagnosis was 44 years, ranging from 28 to 56 years. Abnormal uterine bleeding was the most common intimal symptom (3/8), followed by low back discomfort (2/8), edema of the lower limbs (2/8), abdominal pain (1/8), and dyspnea (1/8). All patients underwent resection of the intravascular and extravascular portions of the tumor. Two patients were in stage IIIC, and six were in stage IVB. After surgery, four patients received adjuvant radiotherapy, of whom three also received letrozole. One patient was treated with letrozole alone, and one patient received medroxyprogesterone. The average follow-up time was 34.5 months, ranging from 6 to 98 months. No patients died or relapsed during the follow-up period.
LG-ESS with intracaval or intracardiac extension is an uncommon type of tumor which is easily misdiagnosed and can only be diagnosed by histological evaluation after surgery. Complete tumoral excision followed by adjuvant therapy may benefit patient survival time. Long-term follow-up is essential due to the high rate of late recurrence.

UNASSIGNED: To compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor ovarian response (POR).
UNASSIGNED: This was a retrospective cohort study. Women with POR who underwent IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2020 and January 2021 were included. The primary outcome measure of our study was the number of oocytes retrieved. The secondary outcome measures in the present study were the number of 2PN, number of available embryos, oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved, cancellation rate and pregnancy outcomes of the first embryo transfer cycle, including the biochemical pregnancy, clinical pregnancy and miscarriage rates.
UNASSIGNED: In total, 118 women underwent hMG +DYG protocols, and 692 women who underwent hMG +MPA met the Bologna criteria for POR. After baseline characteristics were balanced using the PSM model, 118 hMG +DYG protocols were matched to 118 hMG +MPA protocols, and the baseline characteristics were comparable between the two groups. The numbers of oocytes retrieved, 2PN, and available embryos and the oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved and cancellation rate of the hMG+DYG and hMG+MPA protocols were comparable. Altogether, 66 women in the hMG+DYG group and 87 women in the hMG+MPA group underwent first embryo transfers. In the hMG+DYG group, 81.8% (54/66) of the patients underwent cleavage embryo transfers; similarly, 79.3% (69/87) of patients in the hMG+MPA group had cleavage embryo transfers (P=0.70).The biochemical pregnancy rate of the hMG+DYG group was 42.4%, and this was comparable to the rate in the hMG+DYG group, at 34.5% (P=0.32). The clinical pregnancy rates were similar between the two groups (36.4% vs. 31.0%, P=0.49), and there was no significant difference in the rate of miscarriage between the two groups (12.5% vs. 29.6%, P=0.14).
UNASSIGNED: For women with POR, the clinical outcome of the hMG + DYG group was similar to that of the hMG + MPA group, indicating that both combinations can be useful options for PPOS protocols.

Endocrine therapy is a promising treatment for endometrial cancer (EC) that preserves fertility, however, progesterone-resistance is currently the major challenges. The Cancer Genome Atlas (TCGA) database analysis showed that CNR1 was closely have a negative correlation with overall survival (OS) and relapse-free survival (RFS) in endometrial cancer. To explore the role of CNR1 in progesterone resistance and possible molecular regulation mechanism, we established stable progesterone-resistant cell lines (IshikawaPR) via progesterone tolerance of ordinary cancer cells (Ishikawa). The difference of CNR1 level in two cell lines was assessed by MTT, RT-PCR, Western blot, immunofluorescence. Then, lentiviruses constructed CNR1-knockdown with GV248 as the tool vector were used to transfect IshikwaPR cells, and the changes of biological behavior and progesterone sensitivity was verified respectively through plate cloning experiment, EdU assay, flow cytometry cycle analysis, transwell, Scratch test, etc. We founded after CNR1 was knocked down, the proliferative activity and ability to migrate of IshikawaPR cells decreased, progesterone-response sensitivity could be improved. Moreover, knockdown of CNR1 can also down-regulate ERK and NFκ B expression and activation. Furthermore, subcutaneous xenograft in nude mice was tested similarly in vivo. The above datas suggest that targeting CNR1 may reverse the progesterone resistance in endometrial cancer and may coordinate the role of ERK pathway activation.

Fertility preservation is an option for selected patients with endometrial hyperplasia or cancer. This study aimed to evaluate whether duration of treatment impacts the oncologic and reproductive outcomes.
We retrospectively reviewed patients diagnosed with endometrial cancer/atypical endometrial hyperplasia who underwent fertility-sparing treatment from January 2012 to December 2016. As the duration of treatment required by the patients was different, the patients who achieved a complete response were grouped according to the treatment duration as groups A (≤6 months), B (6-9 months), and C (>9 months).
With the prolongation of treatment duration from 6 months to 9 months to >9 months, the accumulative complete response rates for 67 patients were 58%, 76%, and 95.5%, respectively. Among groups A, B, and C there was no significant difference in the relapse rates (21.1%, 25%, and 36.4%, respectively, p=0.60) or the median time interval to relapse (14, 13, and 13.5 months, respectively, p=0.90). Maintenance treatment was an independent protective factor for recurrence (p=0.001), while the complication of diabetes was an independent risk factor for recurrence (p=0.03). Fertility rates (31%, 18.2%, and 62.5%, respectively, p=0.12) and the time interval to pregnancy (14, 13, and 8 months, respectively, p=0.67) were not significantly different among the three groups. Assisted reproductive technology was positively associated with a higher pregnancy rate (p=0.02) and a body mass index ≥25 kg/m2 was negatively associated with the pregnancy rate (p=0.047).
Longer treatment duration was associated with higher rates of complete response. Longer treatment duration (>9 months) was not associated with a decrease in success rates of pregnancy.

Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia. Atypical endometrial hyperplasia suggests a significant pre-malignant state with frank progression to endometrial carcinoma, and tends to occur at a young age. Oral progestins have been used as conservative treatment in young women with atypical endometrial hyperplasia, but they are associated with poor tolerability and side effects that may limit their overall efficacy. So it has become increasingly important and necessary to find a safe and effective fertility-sparing treatment with better tolerability and fewer side effects than the options currently available. The levonorgestrel-releasing intrauterine system (LNG-IUS) has been used to provide endometrial protection in women with breast cancer who are on adjuvant tamoxifen. The antiproliferative function of levonorgestrel is thought to reduce the risk of endometrial hyperplasia.
To determine the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.
In July 2018 we searched CENTRAL; MEDLINE; Embase; CINAHL, PsycINFO and the China National Knowledge Infrastructure for relevant trials. Cochrane Gynaecology and Fertility (CGF) Specialised Register and Embase were searched in November 2018. We attempted to identify trials from references in published studies. We also searched for ongoing trials in five major clinical trials registries.
Randomised controlled trials (RCTs) of oral and intrauterine progestogens (LNG-IUS) versus each other or placebo in women with a confirmed histological diagnosis of simple or complex endometrial hyperplasia with atypia.
Two review authors assessed trial eligibility and risk of bias and extracted the data. The primary outcomes of the review were rate of regression and adverse effects. Secondary outcomes included rate of recurrence and proportion of women undergoing hysterectomy. We have used GRADE methodology to judge the quality of the evidence.
We included one RCT (153 women) comparing the LNG-IUS administering 20 micrograms (μu) levonorgestrel per day versus 10 milligrams of continuous or cyclical oral medroxyprogesterone (MPA) for treating any type of endometrial hyperplasia. Only 19 women in this study were histologically confirmed with atypical complex hyperplasia before treatment. The evidence was of low or very low quality. The included study was at low risk of bias, but the quality of the evidence was very seriously limited by imprecision and indirectness. We did not find any RCTS comparing the LNG-IUS or oral progestogens versus placebo in women with atypical endometrial hyperplasia.Among the 19 women with atypical complex hyperplasia, after six months of treatment there was insufficient evidence to determine whether there was a difference in regression rates between the LNG-IUS group and the progesterone group (odds ratio (OR) 2.76, 95% confidence interval (CI) 0.26 to 29.73; 1 RCT subgroup, 19 women, very low-quality evidence). The rate of regression was 100% in the LNG-IUS group (n = 6/6) and 77% in the progesterone group (n = 10/13).Among the total study population (N = 153), over the six months\' treatment the main adverse effects were nausea and vaginal bleeding. There was no evidence of a difference between the groups in rates of nausea (OR 0.58, 95% CI 0.28 to 1.18; 1 RCT, 153 women, very low-quality evidence). Vaginal bleeding was more common in the LNG-IUS group (OR 2.89, 95% CI 1.11 to 7.52; 1 RCT, 153 women, low-quality evidence). Except for nausea and vaginal bleeding, no other adverse effects were reported.
We did not find any RCTS of women with atypical endometrial hyperplasia, and our findings derive from a subgroup of 19 women in a larger RCT. All six women who used the LNG-IUS system achieved regression of atypical hyperplasia, but there was insufficient evidence to draw any conclusions regarding the relative efficacy of LNG-IUS versus oral progesterone (MPA) in this group of women. When assessed in a population of women with any type of endometrial hyperplasia, there was no clear evidence of a difference between LNG-IUS and oral progesterone (MPA) in risk of nausea, but vaginal bleeding was more likely to occur in women using the LNG-IUS. Larger studies are necessary to assess the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.

OBJECTIVE: To explore the effects of Wnt5a and Wint7a on the differentiation of human embryonic stem cells (hESCs) into endometrium-like cells, and provide a basis for establishing endometrium-like cell models and a cell source for carrying out further endometrium-related experiments.
METHODS: The hESCs established by our center were differentiated into endometrium-like cells in 4 different media including Wnt5a (Group A), Wnt7a (Group B), secreted frizzled related protein (sFRP, an inhibitor of Wnt signal pathway, Group C) and medium alone (Group D). In the differentiated terminal cells, the expressions of cytokeratin (CK) and vimentin were detected with immunofluorescence, and the mRNA levels of CK18, epithelial cell adhesion molecule (EPCAM), estrogen receptor (ER) and progesterone receptor (PR) were determined with RT-PCR. At the same time, the differentiated terminal cells were incubated in medium containing medroxyprogesterone followed by determination of prolactin (PRL).
RESULTS: RT-PCR indicated that mRNA levels of CK18, EPCAM, ER and PR were significantly higher in Group A (Wnt5a) than in other groups (all P<0.05), but were significantly lower in Group C (sFRP2) than in other groups (all P<0.05). The changing trend of PRL mRNA was consistent with that of above genes in the 4 groups. Immunofluorescence displayed that the expression of cytokeratin was the strongest in Group A (Wnt5a), and the weakest in Group C (sFRP2) among the 4 groups.
CONCLUSIONS: Wnt5a has promotive effects on the differentiation of hESCs into endometrium-like cells, but Wnt7a has no marked effects.

OBJECTIVE: To explore the in vitro effects of thioridazine (THIO) plus medroxyprogesterone (MPA) on the proliferation and apoptosis of endometrial cancer cell lines (Ishikawa & KLE) and examine the mechanism in the treatment of endometrial cancer.
METHODS: CCK-8 assay was employed for detecting the influence of THIO plus MPA on the proliferation and apoptosis of endometrial cancer cells (ISK & KLE). And the concentration and timepoints of drugs were determined according to the results. Real-time polymerase chain reaction (PCR) and Western blot were used to detect the expression levels of PRB, DRD2 and p-AKT/AKT in PI3K/AKT signal pathway. Flow cytometry was applied for detecting the apoptosis of combination (THIO+MPA) and MPA groups.
RESULTS: Compared to MPA group, the proliferation inhibiting effect of combination group increased significantly in ISK and KLE cells (52.5% ± 2.6% vs 37.3% ± 0.3%, P < 0.05; 97.7% ± 0.7% vs 50.0% ± 0.4%, P < 0.001); the apoptotic rates increased (34.0% ± 1.4% vs 50.5% ± 2.4%, P < 0.01; 5.5% ± 3.6% vs 11.3% ± 0.7%, P < 0.01); the expression levels of PRB and DRD2 were up-regulated (all P < 0.05). And the ratio of p-AKT/AKT decreased obviously.
CONCLUSIONS: Thioridazine significantly enhances the effects of MPA on proliferative inhibition and apoptotic promotion in endometrial cancer cells. And it may be associated with the PRB/DRD2-mediated PI3K/AKT signal pathway.

BACKGROUND: Goserelin plus aromatase inhibitors (AI) have already been used in male advanced breast cancer, but the cases that fulvestrantin male breast cancer are rare.
METHODS: Here we report a case of long-term (3 years) response to Goserelin plus continuing endocrine treatments given for a male advanced breast cancer. The patient prolongs his life with high life quality, and has more time with his family.
CONCLUSIONS: Goserelin plus endocrine treatments may benefit male breast cancer.

Endometrial decidualization is highly important for successful construction and maintenance of embryo implantation and pregnancy. Lefty gene at different menstrual cycle phases has different expressions, indicating its regulatory significance. To study the mechanism of Lefty in decidualization, human endometrial stromal cells (hESCs) were cultured and induced with medroxyprogesterone acetate (MPA) and 8-bromoadenosine-cAMP (8-Br-cAMP) in vitro as a research model. Our results showed that Lefty1 overexpression inhibited MPA- and 8-Br-cAMP-induced hESC decidualization and significantly reduced the secretion of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP-1). With the inhibition of Lefty1 expression, hESC decidualization induced by MPA and 8-Br-cAMP became more remarkable, and the secretions of PRL and IGFBP-1 were higher too. Further tests indicated that during the process of decidualization, P57 expression increased, whereas cyclin D1 expression decreased. Although Lefty1 overexpression did not significantly change the expressions of P57 and cyclin D1, inhibition of Lefty1 expression resulted in more evident changes in P57 and cyclin D1 expressions. Meanwhile, cell cycle examination showed that Lefty1 overexpression reduced the cell cycle arrest at G1/S phase in the in vitro hESC decidualization model. Therefore, Lefty1 could regulate the cell cycle via modulating the expressions of P57 and cyclin D1 and then inhibit the decidualization in vitro.