Mismatch repair deficiency and abnormal p53 expression has significant predictive value for progesterone resistance and endometrial tumorigenesis in patients with endometrial atypical hyperplasia receiving fertility-preserving treatment.

OBJECTIVE: This study aimed to evaluate the prognostic ability of mismatch repair deficiency (MMR-d) and abnormal p53 expression (p53abn) in patients with endometrial atypical hyperplasia (EAH) who underwent fertility-preserving treatment. METHODS: This retrospective study evaluated 51 patients with EAH who underwent fertility-sparing treatment. Endometrial biopsy specimens obtained before hormone therapy were collected and used for immunohistochemical staining for MMR and p53 proteins. Response, relapse, and progression rates were assessed based on age, body mass index, diabetes, polycystic ovary syndrome, reproductive history, MMR status, and p53 status. RESULTS: Overall, 11/51 (21.6%) patients had loss of MMR proteins and 6/51 (11.8%) had p53abn. Patients with MMR-d had lower complete response (CR) rates than those with normal staining patients at 12 months after initial treatment (p = 0.049). Patients with MMR-d had significantly higher relapse rates than those with MMR-p at the 1-year follow-ups after achieving CR (p = 0.035). Moreover, patients with MMR-d had a higher incidence of disease progression at 2, 3, and 4 years after fertility-sparing treatment (p = 0.001, p = 0.01 and p = 0.035, respectively). Patients with p53abn had higher relapse rates than those with p53wt at the 1- and 2-year follow-ups after achieving CR (p = 0.047 and p = 0.036, respectively). Moreover, patients with p53abn had a higher incidence of disease progression at 3 and 4 years after fertility-sparing treatment (p = 0.02 and p = 0.049, respectively). CONCLUSIONS: EAH patients with MMR-d and p53abn have a significantly higher risk of disease relapse and progression. Thus, MMR-d and p53abn may be used as predictive biomarkers of progestin resistance and endometrial tumorigenesis in EAH.

Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta-analysis.

INTRODUCTION: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). RESULTS: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). CONCLUSIONS: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.

Recurrent endometrial atypical hyperplasia diagnosed by pathological examination of the placenta from a live birth: a case report.

BACKGROUND: Pregnancy complicated with endometrial atypical hyperplasia, which is often observed during early pregnancy, is extremely rare. CASE PRESENTATION: The patient was a 30-year-old woman who had premature delivery at 30+ 1 weeks gestation, and endometrial atypical hyperplasia was discovered by placental examination. CONCLUSIONS: For patients who undergo fertility-sparing treatment for endometrial atypical hyperplasia, the evaluation of the decidua via the placental pathological examination is particularly important. These examinations make a great clinical contribution to the early detection and diagnosis of endometrial atypical hyperplasia.

Obstetric and perinatal outcomes following frozen and fresh embryo transfer in patients with endometrial hyperplasia and carcinoma: a retrospective study in a high-volume reproductive center.

BACKGROUND: There is ongoing debate regarding which embryo transfer procedure can achieve a higher live birth rate. Research has suggested that frozen ET might be beneficial for certain populations, such as hyper-responders. This study aimed to compare outcomes of pregnancies between frozen and fresh embryo transfer cycles in patients with endometrial hyperplasia and carcinoma. METHODS: This retrospective cohort study was conducted at a high-volume reproductive center from January 2010 to January 2022. Patients who were diagnosed with endometrial hyperplasia with atypia and endometrial carcinoma were included. They all underwent in vitro fertilization after conservative treatment. The primary outcome was live birth after frozen and fresh embryo transfer cycles, and secondary outcomes included perinatal complications and other pregnancy outcomes. RESULTS: Overall, 259 ET cycles (130 fresh and 129 frozen) were included. The rate of live births per embryo transfer cycle of the whole cohort was 20.8% (54/259), and no significant between-group difference was found after adjusting for potential confounding factors (23.8% vs. 17.8%; adjusted OR, 0.47; 95% CI, 0.21-1.06; p=0.068). Compared to fresh embryo transfer group, the incidence of total maternal complications in the frozen embryo transfer group was significantly higher (30.4% vs. 6.5%, p=0.019). Analyzing each complication as a separate entity, patients in the frozen embryo transfer group had a higher incidence of hypertensive disorders of pregnancy (p=0.028). Multiple logistic regression analysis showed that frozen embryo transfer was related with an increased occurrence of maternal complications (OR, 6.68, 95% CI, 1.01-44.19, p=0.040). CONCLUSIONS: Among patients with endometrial hyperplasia and carcinoma, the rate of live births was comparable between both embryo transfer procedures, while frozen embryo transfer might be associated with a higher risk of maternal complications compared to that with fresh embryo transfer.

Analysis of immunohistochemical characteristics and recurrence after complete remission with fertility preservation treatment in patients with endometrial carcinoma and endometrial atypical hyperplasia.

OBJECTIVE: To investigate the relationship between immunohistochemical characteristics and recurrence after complete remission (CR) with fertility preservation treatment in patients with endometrial cancer (EC) and endometrial atypical hyperplasia (AH). METHODS: The clinical data and immunohistochemical results of 53 patients with EC and 68 patients with AH admitted to Peking University People's Hospital from January 2010 to January 2021 were retrospectively analyzed. Patients were divided into two groups according to whether recurrence after complete remission (CR): group 1: recurrence after CR; group 2: no recurrence after CR, for statistical analysis. RESULTS: (1) The expression rate of ER in group 1 was lower than that in group 2, (P < 0.05). The expression rate of Ki-67 in group 1 was significantly higher than that in group 2, (P < 0.01). The expression rates of PR, P16, P53, and PTEN were not significantly different between the two groups (P > 0.05); (2) combination index ER/ Ki-67 row ROC curve analysis, there was a significant difference (P < 0.01), the best cut-off value was 3.55, sensitivity 0.730, specificity 1.000, Youden index 0.730. The 3-year RFS of high rate patients was 100%, and that of low rate patients was 42.3%, P < 0.01. CONCLUSIONS: The expression rate of Ki-67 is of great significance in predicting the recurrence of EC after fertility preservation therapy. The best cut-off value of combination index ER/ Ki-67 (3.55) was better than a single immunohistochemical marker in predicting recurrence of EC after fertility preservation treatment.

Efficacy and pregnancy outcomes of hysteroscopic surgery combined with progestin as fertility-sparing therapy in patients with early stage endometrial cancer and atypical hyperplasia.

PURPOSE: This study aims to evaluate the efficacy of hysteroscopic curettage combined with progestin therapy in young patients with early-stage endometrial cancer (EC) and endometrial atypical hyperplasia (EAH) who wished to preserve their fertility. METHODS: This prospective cohort study included 16 patients with early-stage EC and 25 patients with EAH in Dalian Maternal and Child Health Hospital from August 2014 to October 2018. All patients received fertility-sparing therapy with hysteroscopic evaluation every 3 months until achieving complete response (CR). Demographic, clinical, and pathological data follow-up information as well as fertility outcomes was analyzed. RESULTS: There were 92.6% (37/41) patients who achieved CR. The mean treatment duration to CR was 7.47 ± 2.91 months. BMI ≤ 30 kg/m2 was associated with shorter treatment duration to achieve CR (P = 0.003). Among the patients who attempted to conceive, 30.3% (10/33) had successful pregnancy, and 18.2% (6/33) delivered live births. The implementation of assisted reproductive technology (ART) is closely associated with pregnancy (P = 0.001). CONCLUSION: The fertility-sparing therapy, hysteroscopic curettage combined with progestin therapy, of early young EC and EAH patients is safe and effective. BMI is the main factor affecting the duration of CR. After achieving CR, ART can significantly improve the pregnancy rate of these patients.

Correlation of plasma adipokines with endometrial atypical hyperplasia and type I/II endometrial cancer.

The aim of the study was to systematically explore the relationships between various adipokines and risks of endometrial atypical hyperplasia (EAH), type I endometrial cancer (EC), and type II EC. We enrolled 219 patients in this study, including 39 EAH, 87 type I EC, 38 type II EC and 55 control individuals. We subsequently explored the association of adipokine levels and the leptin-to-adiponectin (L/A) ratio with EAH, type I EC, and type II EC. The plasma leptin level and L/A ratio were significantly higher in the EAH group than in the control group (p = 0.012). Leptin, resistin, vaspin, and visfatin levels were significantly higher in the type I EC group; however, the adiponectin level was lower in the type I EC, which resulted in a higher L/A ratio. Notably, the L/A ratio and visfatin level in the type II EC group were significantly higher. Multiple logistic regression analysis revealed that a higher leptin level was significantly associated with a higher EAH risk (p = 0.012). Higher leptin level (p = 0.042) and L/A ratio (p = 0.027) were significantly associated with an increased type I EC risk. By contrast, higher leptin (p = 0.059) and visfatin (p = 0.003) levels, higher L/A ratio (p = 0.033), and lower adiponectin level (p = 0.042) were associated with an increased type II EC risk. We suggested that adipokines are potentially correlated with EAH and EC risks.

What is already known on this subject? EAH and EC are considered significantly correlated with obesity and the related insulin resistance. Studies reported that some of the adipokines mediate obesity-related EC risk.What do the results of this study add? We systematically explored whether the adipokines produced from adipose tissue, including leptin, adiponectin, resistin, vaspin, and visfatin as well as the L/A ratio were associated with increased EAH, type I EC, and type II EC risks; whether they are independent risk factors for EAH and EC. Moreover, we analysed the underlying roles of these adipokines in EC tumorigenesis and development.What are the implications of these findings for clinical practice and/or further research? This study aimed to systematically explore the relationships between various adipokines and risks of EAH, type I EC, and type II EC, to suggest that adipokine levels correlated with EAH and EC risks, and to analyse the underlying molecular mechanisms linking adipokines with endometrial carcinogenesis. It is helpful to improve our understanding of EC tumorigenesis and development.

Histopathologic diagnosis of endometrial precancers: Updates and future directions.

Early detection of endometrial cancer, especially its precancers, remains a critical and evolving issue in patient management and the quest to decrease mortality due to endometrial cancer. Due to many factors such as specimen fragmentation, the confounding influence of endogenous or exogenous hormones, and variable or overlapping histologic features, identification of bona fide endometrial precancers and their reliable discrimination from benign mimics remains one of the most challenging areas in diagnostic pathology. At the same time, the diagnosis of endometrial precancer, or the presence of suspicious but subdiagnostic features in an endometrial biopsy, can lead to long clinical follow-up with multiple patient visits and serial endometrial sampling, emphasizing the need for accurate diagnosis. Our understanding of endometrial precancers and their diagnosis has improved due to systematic investigations into morphologic criteria, the molecular genetics of endometrial cancer and their precursors, the validation of novel biomarkers and their use in panels, and more recent methods such digital image analysis. Although precancers for both endometrioid and non-endometrioid carcinomas will be reviewed, emphasis will be placed on the former. We review these advances and their relevance to the histopathologic diagnosis of endometrial precancers, and the recently updated 2020 World Health Organization (WHO) Classification of Female Genital Tumors.

Conservative Management of Atypical Endometrial Hyperplasia and Early Endometrial Cancer in Childbearing Age Women.

Total hysterectomy and bilateral adnexectomy is the standard treatment for atypical endometrial hyperplasia and early-stage endometrial cancer. However, the recommended surgical treatment precludes future pregnancy when these conditions are diagnosed in women in their fertile age. In these patients, fertility-sparing treatment may be feasible if the desire for childbearing is consistent and specific conditions are present. This review summarizes the available evidence on fertility-sparing management for atypical endometrial hyperplasia and early-stage endometrial cancer. Historically, oral progestins have been the mainstay of conservative management for atypical endometrial hyperplasia and stage IA endometrioid endometrial cancer with no myometrial invasion, although there is no consensus on dosage and treatment length. Intrauterine progestin therapy has proved a valid alternative option when oral progestins are not tolerated. GnRH analogs, metformin, and hysteroscopic resection in combination with progestins appear to increase the overall efficacy of the treatment. After a complete response, conception is recommended; alternatively, maintenance therapy with strict follow-up has been proposed to decrease recurrence. The risk of disease progression is not negligible, and clinicians should not overlook the risk of hereditary forms of the disease in young patients, in particular, Lynch syndrome. Hysterectomy is performed once the desire for childbearing desire has been established. The conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer is feasible, provided a strong desire for childbearing and permitting clinical-pathological conditions. However, patients must be aware of the need for a strict follow-up and the risk of progression with a possible consequent worsening of the prognosis. More homogenous and well-designed studies are necessary to standardize and identify the best treatment and follow-up protocols.

IVF impact on the risk of recurrence of endometrial adenocarcinoma after fertility-sparing management.

RESEARCH QUESTION: Do IVF treatments after conservative management of endometrial atypical hyperplasia or grade 1 endometrial adenocarcinoma (AH/EC) increase the risk of disease recurrence? DESIGN: This is a prospective cohort study from a national registry from January 2008 to July 2019. Sixty patients had an AH/EC and received progestin treatment using chlormadinone acetate for at least 3 months. After remission, 31 patients underwent IVF and 29 did not. The primary outcome was the recurrence rate at 24 months according to the use of IVF. The secondary outcome was the identification of risk factors for recurrence. RESULTS: The probability of 2-year recurrence was 37.7% (SD 10.41%) in the IVF group and 55.7% (SD 14.02%) in the no IVF group (P = 0.13). Obesity, nulliparity, polycystic ovary syndrome, age and tumoural characteristics were not associated with recurrence. Pregnancy was a protective factor for recurrence, with 2-year recurrence probabilities of 20.5% and 62.0% in the pregnancy and no pregnancy groups, respectively (P = 0.002, 95% CI 0.06-0.61). In contrast, the number of cycles, maximum serum oestradiol concentration during ovarian stimulation, ovarian stimulation protocol, total dose of gonadotrophin administered and thickness of the endometrium showed no significant differences in terms of the risk of recurrence in the IVF subgroup. CONCLUSION: IVF treatment after fertility-sparing management of AH/EC does not increase the risk of recurrence. Therefore, it is an acceptable strategy to decrease the time to pregnancy. Overall, the recurrence rate is high enough to justify close monitoring once remission occurs.

Significance of serum and pathological biomarkers in fertility-sparing treatment for endometrial cancer or atypical hyperplasia: a retrospective cohort study.

BACKGROUND: This study analyzed the changes of serum and pathological biomarkers during fertility-sparing therapy of endometrial cancer (EC) or endometrial atypical hyperplasia (EAH), to investigate their implications for early prediction of treatment efficacy. METHODS: A retrospective analysis of EC or EAH patients who received fertility-sparing therapy between 2012 and 2016 was performed. Serum and endometrium sampling were obtained for each patient at three time points: at baseline, at 3-6 months' treatment and at the end of conservative treatment. Serum biomarkers including insulin resistance (HbA1c, HOMA-IR), sex hormones and thyroid hormones were measured. Meanwhile expression of endometrial pathological biomarkers including ER, PR, PRB and Ki-67 was also assessed by immunohistochemistry. RESULTS: For the 53 recruited patients, overall complete response, recurrence and pregnancy rates were 94%, 26% and 36.4%. During the treatment, the serum biomarkers of HOMA-IR remained stable, while pathological markers including PR, PRB and Ki67 diminished significantly. Patients who achieved remission faster had significant lower HOMA-IR level and higher PRB expression at baseline. We also found a more remarkable down-regulation of PRB related with faster remission. Further multivariate analysis confirmed that baseline HOMA-IR ≥ 2.5 negatively affected treatment time to remission (OR 0.206; p = 0.017). While marked reduction of PRB (≥ 30%) at 3-6 months' treatment correlated with faster remission (OR 5.788; p = 0.010). CONCLUSION: For EC and EAH patients who received fertility-sparing therapy, baseline status of insulin resistance predicted poor response to progestin, while marked reduction of PRB following the initial 3-6 months' treatment predicted fast remission.

18F-FDG PET/CT Quantitative Parameters and Texture Analysis Effectively Differentiate Endometrial Precancerous Lesion and Early-Stage Carcinoma.

OBJECTIVE: This study evaluated the metabolic parameters and texture features of fluorodeoxyglucose positron emission tomography-computed tomography (PET/CT) for the diagnosis and differentiation of endometrial atypical hyperplasia (EAH), EAH with field cancerization (FC), and stage 1A endometrial carcinoma (EC 1a). MATERIALS AND METHODS: We retrospectively analyzed the metabolic parameters of PET/CT in 170 patients with diagnoses confirmed by pathology, including 57 cases of EAH (57/170, 33.53%), 45 cases of FC (45/170, 26.47%), and 68 cases of EC 1a (68/170, 40.0%). Then, the texture features of each tumor were extracted and compared with the metabolic parameters and pathological results using nonparametric tests and linear regression analysis. The diagnostic performance was assessed by the area under the curve (AUC) values obtained from receiver operating characteristic analysis. RESULTS: There were moderate positive correlations between the PET standardized uptake values (SUVpeak, SUVmax, and SUVmean) and postoperative pathological features with correlation coefficients (rs) of 0.663, 0.651, and 0.651, respectively (P < .001). Total lesion glycolysis showed relatively low correlation with pathological characteristics (rs = 0.476), whereas metabolic tumor volume and age showed the weakest correlations (rs = 0.186 and 0.232, respectively). To differentiate between the diagnosis of EAH and FC, SUVmax displayed the largest AUC of 0.857 (sensitivity, 82.2%; specificity, 84.2%). Five texture features were screened out as Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 (P < .001) by linear model of texture analysis (AUC = 0.851; specificity = 0.692; sensitivity = 0.871). To differentiate between the diagnoses of FC and EC 1a, SUVpeak displayed the largest AUC of 0.715 (sensitivity, 67.6%; specificity, 77.8%), and 2 texture features were identified as Percentile 10 and CP_angle 135_offset 7 (AUC = 0.819; specificity = 0.871; sensitivity = 0.766; P < .001). CONCLUSIONS: SUVmax and SUVpeak had the highest diagnostic values for EAH, FC, and EC 1a compared with the other tested parameters. SUVmax, Percentile 40, Percentile 45, InverseDifferenceMoment_AllDirection_offset 1, InverseDifferenceMoment_angle 45_offset 4, and ClusterProminence_angle 135_offset 7 distinguished EAH from FC. SUVpeak, Percentile 10, and ClusterProminence_angle 135_offset 7 distinguished FC from EC 1a. This study showed that the addition of texture features provides valuable information for differentiating EAH, FC, and EC 1a diagnoses.

Treatment efficiency of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young women with endometrial atypical hyperplasia and endometrial cancer.

OBJECTIVE: This study aimed to evaluate the efficacy of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young patients with endometrial atypical hyperplasia (EAH) and early stage endometrial cancer (EEC) who wished to preserve their fertility. METHODS: Patients with EAH (n = 120) or well-differentiated EEC (n = 40, FIGO stage IA, without myometrial invasion) were retrospectively included. All patients received constant oral progestin combined with hysteroscopic evaluation every 3 months until achieving complete response (CR). The location, number and size of each suspected lesion or cluster were detailly recorded during the hysteroscopy. RESULTS: The median age was 32.0 year-old (range, 22-47 year-old). Totally 148 patients (97.4%) achieved CR while 3 EAH and 1 EEC patients presented with disease progression, and 8 patients were still in treatment. The mean treatment duration for achieving CR was 6.7 ±â€¯0.3 months (range, 1-18 months). After adjusting for patient age, body mass index (BMI), history of pregnancy and type of conservative therapies, lesion size ≤2 cm (OR, 0.701; 95% CI, 0.496-0.991; P = 0.045) was significantly correlated with shorter treatment time to achieve CR. Among 60 patients attempted to conceive after achieving CR, 45.0% (15/60) had been pregnant, 25.0% (15/60) delivered live birth, 13.3% (8/60) are still in pregnancy, while 6.7% experienced spontaneous abortion. CONCLUSION: Comprehensive hysteroscopic evaluation and lesion resection plus progestin therapy seem to be an effective and safe fertility sparing therapy for patients with EAH or EEC. Endometrial lesion size ≤2 cm correlated with a shorter treatment period to achieve CR.

The utility of sentinel lymph node mapping in the management of endometrial atypical hyperplasia.

OBJECTIVES: To determine the risk of endometrial cancer (EC) and lymph node involvement in patients with a preoperative diagnosis of "AH-only" versus "AH - cannot rule out carcinoma" and to study the value of SLN mapping. METHODS: We reviewed all patients with a preoperative diagnosis of atypical hyperplasia, who underwent primary surgery with SLN mapping followed by pelvic lymphadenectomy. Sensitivity and negative predictive value (NPV) of SLN and rates of endometrial cancer were calculated. RESULTS: Overall, 64/120 (53.3%) patients were found to have EC on final pathology: 58 stage IA, 3 IB, and 3 IIIC1. In patients with preoperative diagnosis of "AH", 44.3% (31/70) had EC on final pathology compared to 66% (33/50) in patients with "AH - cannot rule out cancer" (p=0.02). Overall, 3.3% of the patients (4/120) had lymph node involvement. In patients with EC with a pre-operative diagnosis of "AH", none had lymph node metastasis (0/31), compared to 12.1% (4/33) in patients with "AH - cannot rule out cancer" (p=0.06). Elevated preoperative CA125 levels (>25U/mL) were statistically associated with the risk of lymph node metastasis on final pathology (p=0.024). Unilateral and bilateral SLN detection occurred in 93.7% and 78.1% respectively. In patients with EC and bilateral SLN mapping, sensitivity and NPV were respectively 66.6% and 97.9%. There was one false negative (ITCs in non-SLN). CONCLUSION: Our data indicate that the risk of lymph node involvement in patients with a preoperative diagnosis of "AH-only" is null. Lymph node assessment could be omitted in those patients. Conversely this risk is significant in patients with "AH - cannot rule out cancer". SLN mapping could be a valuable staging procedure in these patients.

Prognostic factors of oncological and reproductive outcomes in fertility-sparing treatment of complex atypical hyperplasia and low-grade endometrial cancer using oral progestin in Chinese patients.

OBJECTIVE: To evaluate the efficacy and fertility outcomes of progestin treatment for complex atypical hyperplasia (CAH)/grade I endometrial cancer (G1EC) in Chinese patients (≤40years old). METHODS: Women ≤40years old who were treated with progestin for CAH or G1EC were identified from 9 provinces of China. The time to achieve complete response (CR) and the time from CR to recurrence or pregnancy were censored for patients without events and were analyzed for associations between patient and treatment characteristics. RESULTS: Thirty-two patients were included: 13 with CAH and 19 with G1EC. Nine patients exhibited elevated serum HbA1C before treatment. After a mean follow-up of 32.5months, the CR rate was 84.4%. Patients who exhibited elevated HbA1C were more likely to experience CR, while those with polycystic ovarian syndrome (PCOS) exhibited the opposite outcome (p=0.01, 0.03). Nine of 21 patients experienced clinical pregnancies. Eight patients underwent assisted reproductive technology (ART). Five patients had newborn infants. Patients undergoing ART were more likely to become pregnant (p=0.04). CONCLUSION: Oral progestin is an effective fertility-sparing treatment for women with CAH/G1EC in China. Patients with elevated HbA1C receiving both metformin and progestin were more likely to achieve CR, whereas those with PCOS were not. ART is a good choice for clinical pregnancy after treatment.

Impact of obesity on the results of fertility-sparing management for atypical hyperplasia and grade 1 endometrial cancer.

OBJECTIVES: The aim of the present study was to evaluate the impact of obesity on reproductive and oncologic outcomes on the success of fertility-sparing management. METHODS: This retrospective multicenter cohort study included women treated conservatively for atypical hyperplasia (AH) and endometrial cancer (EC) to preserve fertility. Five inclusion criteria were defined: (i) the presence of AH or grade 1 EC confirmed by two pathologists; (ii) adequate radiological examination before conservative management; (iii) available body mass index (BMI) at the beginning of treatment; and (iv) a minimum follow-up time of six months. RESULTS: Forty patients fulfilled the inclusion criteria (17 had EC, and 23 had AH), mean age and BMI were 33 years and 29kg/m(2) respectively. Among the 15 obese patients, after medical treatment, 10 patients responded (67%) and three relapsed, whereas in the 25 non-obese patients, 19 responded (76%) and three relapsed (p=0.72). The overall pregnancy rate and follow-up time were 35% and 35 months respectively. Among the 15 obese patients, after medical treatment, two patients became pregnant, whereas in the 25 non-obese patients, 12 became pregnant (p=0.04). CONCLUSION: Despite similar response and recurrence rates, our results suggest that fertility-sparing management for AH and EC is associated with a lower probability of pregnancy in obese patients.

Fertility sparing treatment of complex atypical hyperplasia and low grade endometrial cancer using oral progestin.

OBJECTIVE: Oral progestin is an alternative to hysterectomy for women with complex atypical hyperplasia (CAH) or grade one endometrial cancer (G1EC) who wish fertility preservation. We evaluated treatment efficacy and fertility outcomes in this population. METHODS: Women <45 y treated with oral progestin for CAH or G1EC were identified from two cancer centers. Data were obtained from medical records and telephone questionnaires. Time until complete response (CR), and from CR until recurrence was censored for patients without events and analyzed for associations with patient and treatment characteristics; cumulative incidence functions were used to estimate event probability over time. RESULTS: 44 patients were identified, 19 (43%) with CAH and 25 (57%) with G1EC. Median age was 36.5 y (26-44). 24 (55%) achieved CR (median time: 5.7 months). Older age was associated with a lower likelihood of CR (HR 0.84, p=0.0003, 95% CI, 0.8-0.9). CR probability appeared to plateau after 12 months of therapy. Among those with CR, 13 (54%) recurred (median time 3.5 y). 24 patients (55%) underwent hysterectomy; 3 (13%) were upstaged. 11 (25%) underwent fertility treatment with the following outcomes: 6 (55%) no pregnancy, 2 (18%) at least one live infant, and 3 (27%) spontaneous abortion. One achieved a live birth without intervention. CONCLUSION: Oral progestin is an effective temporizing fertility-sparing treatment for women with CAH/G1EC. Fertility specialist involvement is recommended due to the low live birth rate without intervention. Progestin therapy should be re-evaluated at 1 year in non-responders due to a low probability of success. Hysterectomy is recommended after childbearing due to a high recurrence rate.

Triglyceride-glucose index (TyG index) and endometrial carcinoma risk: A retrospective cohort study.

OBJECTIVE: We analyzed the association between the triglyceride-glucose index (TyG index) and incident endometrial carcinogenesis, aiming to determine whether the TyG index is a promising predictive biomarker for endometrial carcinoma (EC). METHODS: In this retrospective cohort study, multiple logistic regression analysis was performed to evaluate the relationship between TyG index and EC incidence and progression. The receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC), as well as the cut-off value of the TyG index for EC incidence. RESULTS: The TyG index was significantly higher in patients with EC or endometrial atypical hyperplasia (EAH) than in those with normal endometrium (P < 0.001). A continuous rise was observed in the incidence of EC and EAH among the tertiles of the TyG index (P < 0.001). The multiple logistic regression analysis revealed that the TyG index was associated with EC and EAH risk after adjusting for potential confounding factors (EAH: odds ratio [OR] 2.54, 95% confidence interval [CI] 1.33-4.85, P = 0.005; EC: OR 2.65, 95% CI 1.60-4.41, P < 0.001). Moreover, high TyG index was positively associated with advanced pathological stage (OR 2.14, 95% CI 1.32-3.47, P = 0.002) and poorer differentiation (OR 2.53, 95% CI 1.36-4.72, P = 0.004). CONCLUSION: The TyG index might be a promising biomarker for endometrial carcinogenesis. Subjects with a higher TyG index should be aware of the risk of EC incidence and progression.

Clinicopathological characteristics and fertility preserving treatment of atypical polypoid adenomyoma.

Objective: Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC. Methods: This retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed. Results: The median patient age was 31 years (range 21-47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0-40.4) in the APA group and 26.0 weeks (95% CI: 24.3-32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment. Conclusion: Patients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.

Use of clinicopathological factors to predict prognosis of fertility-sparing treatment for endometrial endometrioid carcinoma and atypical hyperplasia.

The incidence of endometrial endometrioid carcinoma (EEC) has been gradually increasing over the past decade. Fertility-sparing therapy with progestin is a treatment option for EEC or endometrial atypical hyperplasia (AH). The present study evaluated the role of numerous prognostic factors following fertility-sparing therapy for EEC or AH. Furthermore, the present study assessed the strength of various clinicopathological indicators for the prediction of treatment efficacy. A retrospective analysis was performed of patients with EEC and AH who received fertility-sparing therapy between August 2013 and September 2021 at Peking University People's Hospital (Beijing, China). Endometrial specimens were obtained from each patient after 3 months of treatment and at the end of the fertility-sparing therapy, before treatment efficacy and prognosis were evaluated using the χ2 test. Furthermore, the protein expression levels of EEC biomarkers, such as estrogen receptor (ER), progesterone receptor (PR), paired box 2 (PAX2), PTEN and p53 were assessed using immunohistochemistry. The overall complete response (CR) rate of fertility-sparing treatment in the EEC group was 67.39% (31/46), whereas that in the AH group was 86.49% (32/37). The difference between the CR rates in the EEC and AH groups was statistically significant (P<0.05). There was no association between prognosis after treatment and ER, PAX2, PTEN or Ki-67 expression in the initially untreated AH or EEC groups. However, tissues with >50% positive PR expression were demonstrated to have a higher CR rate compared with those with ≤50% positive PR expression in both the EEC and AH groups. Furthermore, the PAX2-positive group tended to demonstrate higher CR rates compared with the PAX2-negative group in the patients with EEC. In conclusion, these data suggested that fertility-sparing therapy is effective for patients with EEC and AH who wish to remain fertile after treatment. Specifically, in the AH group, a higher proportion of patients achieved a CR whilst also achieving this more rapidly. Furthermore, PR was demonstrated to be a useful marker for the evaluation of EEC and AH.